Advertisement

Cell-Translocation Mechanisms of CPPs

  • Ülo Langel
Chapter

Abstract

Our understanding concerning the cellular translocation of CPPs and associated cargos is still widely debatable, being supported by controversial experimental data. In earlier CPP studies, the ideas of direct translocation of CPPs prevailed (Derossi et al. 1994; Pooga et al. 1998), mainly based on experiments demonstrating an even location in the cells of fluorescently labelled CPPs in the fixated cells.

Keywords

Translocation mechanism Direct translocation Endocytosis Binding Signalling Omics 

References

  1. Abdulrahman, B. A., Abdelaziz, D. H., & Schatzl, H. M. (2018). Autophagy regulates exosomal release of prions in neuronal cells. Journal of Biological Chemistry, 293, 8956–8968.PubMedCrossRefPubMedCentralGoogle Scholar
  2. Abes, R., Arzumanov, A. A., Moulton, H. M., Abes, S., Ivanova, G. D., Iversen, P. L., et al. (2007). Cell-penetrating-peptide-based delivery of oligonucleotides: An overview. Biochemical Society Transactions, 35, 775–779.PubMedCrossRefPubMedCentralGoogle Scholar
  3. Al Soraj, M., He, L., Peynshaert, K., Cousaert, J., Vercauteren, D., Braeckmans, K., et al. (2012). siRNA and pharmacological inhibition of endocytic pathways to characterize the differential role of macropinocytosis and the actin cytoskeleton on cellular uptake of dextran and cationic cell penetrating peptides octaarginine (R8) and HIV-Tat. Journal of Controlled Release, 161, 132–141.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Amand, H. L., Rydberg, H. A., Fornander, L. H., Lincoln, P., Norden, B., & Esbjorner, E. K. (2012). Cell surface binding and uptake of arginine- and lysine-rich penetratin peptides in absence and presence of proteoglycans. Biochimica et Biophysica Acta, 1818, 2669–2678.PubMedCrossRefPubMedCentralGoogle Scholar
  5. Arukuusk, P., Pärnaste, L., Hällbrink, M., & Langel, Ü. (2015). PepFects and NickFects for the intracellular delivery of nucleic acids. Methods in Molecular Biology, 1324, 303–315.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Arukuusk, P., Pärnaste, L., Margus, H., Eriksson, N. K., Vasconcelos, L., Padari, K., et al. (2013). Differential endosomal pathways for radically modified peptide vectors. Bioconjugate Chemistry, 24, 1721–1732.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Astrada, S., Fernandez Masso, J. R., Vallespi, M. G. & Bollati-Fogolin, M. (2018). Cell penetrating capacity and internalization mechanisms used by the synthetic peptide CIGB-552 and its relationship with tumor cell line sensitivity. Molecules, 23.Google Scholar
  8. Avci, F. G., Akbulut, B. S. & Ozkirimli, E. (2018). Membrane active peptides and their biophysical characterization. Biomolecules, 8.Google Scholar
  9. Bang, J. Y., Kim, E. Y., Kang, D. K., Chang, S. I., Han, M. H., Baek, K. H., et al. (2011). Pharmacoproteomic analysis of a novel cell-permeable peptide inhibitor of tumor-induced angiogenesis. Molecular and Cellular Proteomics, 10(M110), 005264.PubMedPubMedCentralGoogle Scholar
  10. Barany-Wallje, E., Gaur, J., Lundberg, P., Langel, Ü., & Gräslund, A. (2007). Differential membrane perturbation caused by the cell penetrating peptide Tp10 depending on attached cargo. FEBS Letters, 581, 2389–2393.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Barbieri, E., di Fiore, P. P., & Sigismund, S. (2016). Endocytic control of signaling at the plasma membrane. Current Opinion in Cell Biology, 39, 21–27.PubMedCrossRefPubMedCentralGoogle Scholar
  12. Bechara, C., Pallerla, M., Burlina, F., Illien, F., Cribier, S., & Sagan, S. (2015). Massive glycosaminoglycan-dependent entry of Trp-containing cell-penetrating peptides induced by exogenous sphingomyelinase or cholesterol depletion. Cellular and Molecular Life Sciences, 72, 809–820.PubMedCrossRefPubMedCentralGoogle Scholar
  13. Bechara, C., Pallerla, M., Zaltsman, Y., Burlina, F., Alves, I. D., Lequin, O., et al. (2013). Tryptophan within basic peptide sequences triggers glycosaminoglycan-dependent endocytosis. The FASEB Journal, 27, 738–749.PubMedCrossRefPubMedCentralGoogle Scholar
  14. Bechara, C., & Sagan, S. (2013). Cell-penetrating peptides: 20 years later, where do we stand? FEBS Letters, 587, 1693–1702.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Bell, T. J., & Eberwine, J. (2015a). Live cell genomics: Cell-specific transcriptome capture in live tissues and cells. Methods in Molecular Biology, 1324, 447–456.PubMedCrossRefPubMedCentralGoogle Scholar
  16. Bell, T. J., & Eberwine, J. (2015b). Live cell genomics: RNA exon-specific rna-binding protein isolation. Methods in Molecular Biology, 1324, 457–468.PubMedCrossRefPubMedCentralGoogle Scholar
  17. Benner, N. L., Zang, X., Buehler, D. C., Kickhoefer, V. A., Rome, M. E., Rome, L. H., et al. (2017). Vault nanoparticles: Chemical modifications for imaging and enhanced delivery. ACS Nano, 11, 872–881.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Bernard, K., Litman, E., Fitzpatrick, J. L., Shellman, Y. G., Argast, G., Polvinen, K., et al. (2003). Functional proteomic analysis of melanoma progression. Cancer Research, 63, 6716–6725.PubMedPubMedCentralGoogle Scholar
  19. Binder, H., & Lindblom, G. (2003). Charge-dependent translocation of the Trojan peptide penetratin across lipid membranes. Biophysical Journal, 85, 982–995.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Blaszczyk, M., Harmer, N. J., Chirgadze, D. Y., Ascher, D. B., & Blundell, T. L. (2015). Achieving high signal-to-noise in cell regulatory systems: Spatial organization of multiprotein transmembrane assemblies of FGFR and MET receptors. Progress in Biophysics and Molecular Biology, 118, 103–111.PubMedPubMedCentralCrossRefGoogle Scholar
  21. Bryant, C. E., Symmons, M., & Gay, N. J. (2015). Toll-like receptor signalling through macromolecular protein complexes. Molecular Immunology, 63, 162–165.PubMedCrossRefPubMedCentralGoogle Scholar
  22. Burlina, F., Sagan, S., Bolbach, G., & Chassaing, G. (2006). A direct approach to quantification of the cellular uptake of cell-penetrating peptides using MALDI-TOF mass spectrometry. Nature Protocols, 1, 200–205.PubMedPubMedCentralCrossRefGoogle Scholar
  23. Castanotto, D., Zhang, X., Alluin, J., Zhang, X., Ruger, J., Armstrong, B., et al. (2018). A stress-induced response complex (SIRC) shuttles miRNAs, siRNAs, and oligonucleotides to the nucleus. Proceedings of the National Academy of Sciences of the U S A.Google Scholar
  24. Cedervall, T., Lynch, I., Foy, M., Berggard, T., Donnelly, S. C., Cagney, G., et al. (2007). Detailed identification of plasma proteins adsorbed on copolymer nanoparticles. Angewandte Chemie (International ed. in English), 46, 5754–5756.CrossRefGoogle Scholar
  25. Chen, X., Sa’Adedin, F., Deme, B., Rao, P., & Bradshaw, J. (2013). Insertion of TAT peptide and perturbation of negatively charged model phospholipid bilayer revealed by neutron diffraction. Biochimica et Biophysica Acta, 1828, 1982–1988.PubMedCrossRefPubMedCentralGoogle Scholar
  26. Cheng, T., & Zhan, X. (2017). Pattern recognition for predictive, preventive, and personalized medicine in cancer. The EPMA Journal, 8, 51–60.PubMedPubMedCentralCrossRefGoogle Scholar
  27. Christianson, H. C., & Belting, M. (2014). Heparan sulfate proteoglycan as a cell-surface endocytosis receptor. Matrix Biology, 35, 51–55.PubMedCrossRefPubMedCentralGoogle Scholar
  28. Clavier, S., Illien, F., Sagan, S., Bolbach, G., & Sachon, E. (2016). Proteomic comparison of the EWS-FLI1 expressing cells EF with NIH-3T3 and actin remodeling effect of (R/W)9 cell-penetrating peptide. EuPA Open Proteomics, 10, 1–8.PubMedCrossRefPubMedCentralGoogle Scholar
  29. Clayton, A. H., Atcliffe, B. W., Howlett, G. J., & Sawyer, W. H. (2006). Conformation and orientation of penetratin in phospholipid membranes. Journal of Peptide Science, 12, 233–238.PubMedCrossRefPubMedCentralGoogle Scholar
  30. Collado Camps, E. & Brock, R. (2017). An opportunistic route to success: Towards a change of paradigm to fully exploit the potential of cell-penetrating peptides. Bioorganic and Medicinal Chemistry.Google Scholar
  31. Console, S., Marty, C., Garcia-Echeverria, C., Schwendener, R. & Ballmer-Hofer, K. (2003). Antennapedia and HIV transactivator of transcription (TAT) “protein transduction domains” promote endocytosis of high molecular weight cargo upon binding to cell surface glycosaminoglycans. Journal of Biological Chemistry. United States.Google Scholar
  32. Copolovici, D. M., Langel, K., Eriste, E., & Langel, Ü. (2014). Cell-penetrating peptides: Design, synthesis, and applications. ACS Nano, 8, 1972–1994.PubMedCrossRefPubMedCentralGoogle Scholar
  33. Cosme, P. J., Ye, J., Sears, S., Wojcikiewicz, E. P. & Terentis, A. C. (2018). Label-free confocal raman mapping of transportan in melanoma cells. Molecular Pharmaceutics.Google Scholar
  34. Daigo, Y., Takano, A., Teramoto, K., Chung, S., & Nakamura, Y. (2013). A systematic approach to the development of novel therapeutics for lung cancer using genomic analyses. Clinical Pharmacology and Therapeutics, 94, 218–223.PubMedCrossRefPubMedCentralGoogle Scholar
  35. Daviss, B. (2005). Growing pains for metabolomics. The Scientist, 19, 25–28.Google Scholar
  36. de Simone, F. I., Darbinian, N., Amini, S., Muniswamy, M., White, M. K., Elrod, J. W., et al. (2016). HIV-1 Tat and cocaine impair survival of cultured primary neuronal cells via a mitochondrial pathway. Journal of Neuroimmune Pharmacology, 11, 358–368.PubMedPubMedCentralCrossRefGoogle Scholar
  37. Dempsey, C. E. (1990). The actions of melittin on membranes. Biochimica et Biophysica Acta, 7, 143–161.CrossRefGoogle Scholar
  38. Derossi, D., Calvet, S., Trembleau, A., Brunissen, A., Chassaing, G., & Prochiantz, A. (1996). Cell internalization of the third helix of the Antennapedia homeodomain is receptor-independent. Journal of Biological Chemistry, 271, 18188–18193.PubMedCrossRefPubMedCentralGoogle Scholar
  39. Derossi, D., Joliot, A. H., Chassaing, G., & Prochiantz, A. (1994). The third helix of the Antennapedia homeodomain translocates through biological membranes. Journal of Biological Chemistry, 269, 10444–10450.PubMedPubMedCentralGoogle Scholar
  40. Deshayes, S., Plenat, T., Charnet, P., Divita, G., Molle, G., & Heitz, F. (2006). Formation of transmembrane ionic channels of primary amphipathic cell-penetrating peptides. Consequences on the mechanism of cell penetration. Biochimica et Biophysica Acta, 1758, 1846–1851.PubMedCrossRefPubMedCentralGoogle Scholar
  41. Doherty, G. J., & McMahon, H. T. (2009). Mechanisms of endocytosis. Annual Review of Biochemistry, 78, 857–902.PubMedCrossRefPubMedCentralGoogle Scholar
  42. Doran, P., Wilton, S. D., Fletcher, S., & Ohlendieck, K. (2009). Proteomic profiling of antisense-induced exon skipping reveals reversal of pathobiochemical abnormalities in dystrophic mdx diaphragm. Proteomics, 9, 671–685.PubMedPubMedCentralCrossRefGoogle Scholar
  43. Dowaidar, M., Gestin, M., Cerrato, C. P., Jafferali, M. H., Margus, H., Kivistik, P. A., et al. (2017a). Role of autophagy in cell-penetrating peptide transfection model. Scientific Reports, 7, 12635.PubMedPubMedCentralCrossRefGoogle Scholar
  44. Dowaidar, M., Gestin, M., Cerrato, C., Margus, H., Kivistik, P., Pooga, M., Hällbrink, M. & Langel, Ü. (2017a). Role of autophagy in PepFect14 transfection. Submitted.Google Scholar
  45. Duchardt, F., Fotin-Mleczek, M., Schwarz, H., Fischer, R. & Brock, R. (2007). A comprehensive model for the cellular uptake of cationic cell-penetrating peptides. Traffic, 8, 848–866.Google Scholar
  46. Eggenberger, K., Sanyal, P., Hundt, S., Wadhwani, P., Ulrich, A. S., & Nick, P. (2017). Challenge integrity: The cell-penetrating peptide BP100 interferes with the auxin-actin oscillator. Plant and Cell Physiology, 58, 71–85.PubMedPubMedCentralGoogle Scholar
  47. Eiriksdottir, E., Konate, K., Langel, Ü., Divita, G., & Deshayes, S. (2010). Secondary structure of cell-penetrating peptides controls membrane interaction and insertion. Biochimica et Biophysica Acta, 1798, 1119–1128.PubMedCrossRefPubMedCentralGoogle Scholar
  48. El-Andaloussi, S., Guterstam, P., & Langel, Ü. (2007). Assessing the delivery efficacy and internalization route of cell-penetrating peptides. Nature Protocols, 2, 2043–2047.PubMedCrossRefGoogle Scholar
  49. El-Andaloussi, S., Lehto, T., Mäger, I., Rosenthal-Aizman, K., Oprea, I. I., Simonson, O. E., et al. (2011). Design of a peptide-based vector, PepFect6, for efficient delivery of siRNA in cell culture and systemically in vivo. Nucleic Acids Research, 39, 3972–3987.CrossRefGoogle Scholar
  50. Erazo-Oliveras, A., Najjar, K., Truong, D., Wang, T. Y., Brock, D. J., Prater, A. R., et al. (2016). The late endosome and Its Lipid BMP act as gateways for efficient cytosolic access of the delivery agent dfTAT and Its macromolecular cargos. Cell Chemical Biology, 3, 30120–30129.Google Scholar
  51. Ezzat, K., Helmfors, H., Tudoran, O., Juks, C., Lindberg, S., Padari, K., et al. (2012). Scavenger receptor-mediated uptake of cell-penetrating peptide nanocomplexes with oligonucleotides. The FASEB Journal, 26, 1172–1180.PubMedPubMedCentralCrossRefGoogle Scholar
  52. Falanga, A., Galdiero, M., & Galdiero, S. (2015). Membranotropic cell penetrating peptides: The outstanding journey. International Journal of Molecular Sciences, 16, 25323–25337.PubMedPubMedCentralCrossRefGoogle Scholar
  53. Fan, T. W. M., Lorkiewicz, P. K., Sellers, K., Moseley, H. N. B., Higashi, R. M., & Lane, A. N. (2012a). Stable isotope-resolved metabolomics and applications for drug development. Pharmacology and Therapeutics, 133, 366–391.PubMedCrossRefPubMedCentralGoogle Scholar
  54. Fan, F., Nie, S., Dammer, E. B., Duong, D. M., Pan, D., Ping, L., et al. (2012b). Protein profiling of active cysteine cathepsins in living cells using an activity-based probe containing a cell-penetrating peptide. Journal of Proteome Research, 11, 5763–5772.PubMedCrossRefPubMedCentralGoogle Scholar
  55. Favaro, M. T. P., Serna, N., Sanchez-Garcia, L., Cubarsi, R., Roldan, M., Sanchez-Chardi, A., et al. (2018). Switching cell penetrating and CXCR55-binding activities of nanoscale-organized arginine-rich peptides. Nanomedicine (Lond), 14, 1777–1786.CrossRefGoogle Scholar
  56. Favretto, M. E., Wallbrecher, R., Schmidt, S., van de Putte, R., & Brock, R. (2014). Glycosaminoglycans in the cellular uptake of drug delivery vectors—bystanders or active players? Journal of Controlled Release, 180, 81–90.PubMedCrossRefPubMedCentralGoogle Scholar
  57. Fernandez-Carneado, J., Kogan, M. J., Castel, S., & Giralt, E. (2004). Potential peptide carriers: Amphipathic proline-rich peptides derived from the N-terminal domain of gamma-zein. Angewandte Chemie (International ed. in English), 43, 1811–1814.CrossRefGoogle Scholar
  58. Ferry, X., Brehin, S., Kamel, R., & Landry, Y. (2002). G protein-dependent activation of mast cell by peptides and basic secretagogues. Peptides, 23, 1507–1515.PubMedCrossRefPubMedCentralGoogle Scholar
  59. Fletcher, S., Honeyman, K., Fall, A. M., Harding, P. L., Johnsen, R. D., Steinhaus, J. P., et al. (2007). Morpholino oligomer-mediated exon skipping averts the onset of dystrophic pathology in the mdx mouse. Molecular Therapy, 15, 1587–1592.PubMedCrossRefPubMedCentralGoogle Scholar
  60. Fotin-Mleczek, M., Welte, S., Mader, O., Duchardt, F., Fischer, R., Hufnagel, H., et al. (2005). Cationic cell-penetrating peptides interfere with TNF signalling by induction of TNF receptor internalization. Journal of Cell Science, 118, 3339–3351.PubMedCrossRefPubMedCentralGoogle Scholar
  61. Frankel, A. D., & Pabo, C. O. (1988). Cellular uptake of the tat protein from human immunodeficiency virus. Cell, 55, 1189–1193.PubMedPubMedCentralCrossRefGoogle Scholar
  62. Fretz, M. M., Penning, N. A., Al-Taei, S., Futaki, S., Takeuchi, T., Nakase, I., et al. (2007). Temperature-, concentration- and cholesterol-dependent translocation of L- and D-octa-arginine across the plasma and nuclear membrane of CD34 + leukaemia cells. Biochemical Journal, 403, 335–342.PubMedPubMedCentralCrossRefGoogle Scholar
  63. Fuselier, T., & Wimley, W. C. (2017). Spontaneous membrane translocating peptides: The role of leucine-arginine consensus motifs. Biophysical Journal, 113, 835–846.PubMedPubMedCentralCrossRefGoogle Scholar
  64. Futaki, S., & Nakase, I. (2017). Cell-surface interactions on arginine-rich cell-penetrating peptides allow for multiplex modes of internalization. Accounts of Chemical Research, 50, 2449–2456.PubMedCrossRefPubMedCentralGoogle Scholar
  65. Futaki, S., Nakase, I., Tadokoro, A., Takeuchi, T., & Jones, A. T. (2007). Arginine-rich peptides and their internalization mechanisms. Biochemical Society Transactions, 35, 784–787.PubMedCrossRefPubMedCentralGoogle Scholar
  66. Garcia-Sosa, A. T., Tulp, I., Langel, K., & Langel, Ü. (2014). Peptide-ligand binding modeling of siRNA with cell-penetrating peptides. BioMed Research International, 2014, 257040.PubMedPubMedCentralCrossRefGoogle Scholar
  67. Gasparini, G., Bang, E. K., Montenegro, J., & Matile, S. (2015). Cellular uptake: Lessons from supramolecular organic chemistry. Chemical Communications, 51, 10389–10402.PubMedCrossRefPubMedCentralGoogle Scholar
  68. Gerbal-Chaloin, S., Gondeau, C., Aldrian-Herrada, G., Heitz, F., Gauthier-Rouviere, C., & Divita, G. (2007). First step of the cell-penetrating peptide mechanism involves Rac1 GTPase-dependent actin-network remodelling. Biology of the Cell, 99, 223–238.PubMedCrossRefPubMedCentralGoogle Scholar
  69. Gestin, M., Dowaidar, M., & Langel, U. (2017). Uptake Mechanism of Cell-Penetrating Peptides. Advances in Experimental Medicine and Biology, 1030, 255–264.PubMedCrossRefPubMedCentralGoogle Scholar
  70. Graziani, G. & Lacal, P. M. (2015). Neuropilin-1 as Therapeutic Target for Malignant Melanoma. Front Oncol, 5.Google Scholar
  71. Guarnieri, D., Melone, P., Moglianetti, M., Marotta, R., Netti, P. A., & Pompa, P. P. (2017). Particle size affects the cytosolic delivery of membranotropic peptide-functionalized platinum nanozymes. Nanoscale, 9, 11288–11296.PubMedCrossRefPubMedCentralGoogle Scholar
  72. Gump, J. M., June, R. K., & Dowdy, S. F. (2010). Revised role of glycosaminoglycans in TAT protein transduction domain-mediated cellular transduction. Journal of Biological Chemistry, 285, 1500–1507.PubMedCrossRefPubMedCentralGoogle Scholar
  73. Guterstam, P., Madani, F., Hirose, H., Takeuchi, T., Futaki, S., el Andaloussi, S., et al. (2009). Elucidating cell-penetrating peptide mechanisms of action for membrane interaction, cellular uptake, and translocation utilizing the hydrophobic counter-anion pyrenebutyrate. Biochimica et Biophysica Acta, 1788, 2509–2517.PubMedCrossRefPubMedCentralGoogle Scholar
  74. Hakata, Y., Tsuchiya, S., Michiue, H., Ohtsuki, T., Matsui, H., Miyazawa, M., et al. (2015). A novel leucine zipper motif-based hybrid peptide delivers a functional peptide cargo inside cells. Chemical Communications (Cambridge, England), 51, 413–416.CrossRefGoogle Scholar
  75. Hassane, F. S., Abes, R., el Andaloussi, S., Lehto, T., Sillard, R., Langel, Ü., et al. (2011). Insights into the cellular trafficking of splice redirecting oligonucleotides complexed with chemically modified cell-penetrating peptides. Journal of Controlled Release, 153, 163–172.PubMedCrossRefPubMedCentralGoogle Scholar
  76. Herbig, M. E., Assi, F., Textor, M., & Merkle, H. P. (2006). The cell penetrating peptides pVEC and W2-pVEC induce transformation of gel phase domains in phospholipid bilayers without affecting their integrity. Biochemistry, 45, 3598–3609.PubMedCrossRefPubMedCentralGoogle Scholar
  77. Herce, H. D., Garcia, A. E. & Cardoso, M. C. (2014a). Fundamental Molecular Mechanism for the Cellular Uptake of Guanidinium-Rich Molecules. Journal of the American Chemical Society,  https://doi.org/10.1021/ja507790z.PubMedPubMedCentralCrossRefGoogle Scholar
  78. Herce, H. D., Garcia, A. E., & Cardoso, M. C. (2014b). Fundamental molecular mechanism for the cellular uptake of guanidinium-rich molecules. Journal of the American Chemical Society, 136, 17459–17467.PubMedPubMedCentralCrossRefGoogle Scholar
  79. Hirose, H., Takeuchi, T., Osakada, H., Pujals, S., Katayama, S., Nakase, I., et al. (2012). Transient focal membrane deformation induced by arginine-rich peptides leads to their direct penetration into cells. Molecular Therapy, 20, 984–993.PubMedPubMedCentralCrossRefGoogle Scholar
  80. Howl, J., & Jones, S. (2015a). Cell penetrating peptide-mediated transport enables the regulated secretion of accumulated cargoes from mast cells. Journal of Controlled Release, 202, 108–117.PubMedPubMedCentralCrossRefGoogle Scholar
  81. Howl, J., & Jones, S. (2015b). Insights into the molecular mechanisms of action of bioportides: A strategy to target protein-protein interactions. Expert Reviews in Molecular Medicine, 17, e1.PubMedPubMedCentralCrossRefGoogle Scholar
  82. Howl, J., & Jones, S. (2015c). Protein mimicry and the design of bioactive cell-penetrating peptides. Methods in Molecular Biology, 1324, 177–190.PubMedPubMedCentralCrossRefGoogle Scholar
  83. Hyvonen, M., & Laakkonen, P. (2015). Identification and characterization of homing peptides using in vivo peptide phage display. Methods in Molecular Biology, 1324, 205–222.PubMedPubMedCentralCrossRefGoogle Scholar
  84. Illien, F., Rodriguez, N., Amoura, M., Joliot, A., Pallerla, M., Cribier, S., et al. (2016). Quantitative fluorescence spectroscopy and flow cytometry analyses of cell-penetrating peptides internalization pathways: Optimization, pitfalls, comparison with mass spectrometry quantification. Sci Rep, 6, Doi: 10.1038.Google Scholar
  85. Irannejad, R., Tsvetanova, N. G., Lobingier, B. T., & von Zastrow, M. (2015). Effects of endocytosis on receptor-mediated signaling. Current Opinion in Cell Biology, 35, 137–143.PubMedPubMedCentralCrossRefGoogle Scholar
  86. Jafurulla, M., Tiwari, S., & Chattopadhyay, A. (2011). Identification of cholesterol recognition amino acid consensus (CRAC) motif in G-protein coupled receptors. Biochemical and Biophysical Research Communications, 404, 569–573.PubMedCrossRefPubMedCentralGoogle Scholar
  87. Jan Akhunzada, M., Chandramouli, B., Bhattacharjee, N., Macchi, S., Cardarelli, F., & Brancato, G. (2017). The role of Tat peptide self-aggregation in membrane pore stabilization: Insights from a computational study. Physical Chemistry Chemical Physics: PCCP, 19, 27603–27610.PubMedCrossRefPubMedCentralGoogle Scholar
  88. Jiao, C. Y., Delaroche, D., Burlina, F., Alves, I. D., Chassaing, G., & Sagan, S. (2009). Translocation and endocytosis for cell-penetrating peptide internalization. Journal of Biological Chemistry, 284, 33957–33965.PubMedPubMedCentralCrossRefGoogle Scholar
  89. Johansson, H. J., el Andaloussi, S., Holm, T., Mäe, M., Jänes, J., Maimets, T., et al. (2008). Characterization of a novel cytotoxic cell-penetrating peptide derived from p14ARF protein. Molecular Therapy, 16, 115–123.PubMedPubMedCentralCrossRefGoogle Scholar
  90. Johansson, H. J., El Andaloussi, S., & Langel, Ü. (2011). Mimicry of protein function with cell-penetrating peptides. Methods in Molecular Biology, 683, 233–247.PubMedCrossRefPubMedCentralGoogle Scholar
  91. Juks, C., Lorents, A., Arukuusk, P., Langel, U., & Pooga, M. (2017). Cell-penetrating peptides recruit type A scavenger receptors to the plasma membrane for cellular delivery of nucleic acids. The FASEB Journal, 31, 975–988.PubMedCrossRefPubMedCentralGoogle Scholar
  92. Juks, C., Padari, K., Margus, H., Kriiska, A., Etverk, I., Arukuusk, P., et al. (2015). The role of endocytosis in the uptake and intracellular trafficking of PepFect14-nucleic acid nanocomplexes via class A scavenger receptors. Biochimica et Biophysica Acta, 12, 25.Google Scholar
  93. Kabelka, I. & Vacha, R. (2018). Optimal Hydrophobicity and reorientation of amphiphilic peptides translocating through membrane. Biophys Journal.Google Scholar
  94. Kaitsuka, T., & Tomizawa, K. (2015). Cell-penetrating peptide as a means of directing the differentiation of induced-pluripotent stem cells. International Journal of Molecular Sciences, 16, 26667–26676.PubMedPubMedCentralCrossRefGoogle Scholar
  95. Kamper, N., Day, P. M., Nowak, T., Selinka, H. C., Florin, L., Bolscher, J., et al. (2006). A membrane-destabilizing peptide in capsid protein L2 is required for egress of papillomavirus genomes from endosomes. Journal of Virology, 80, 759–768.PubMedPubMedCentralCrossRefGoogle Scholar
  96. Kang, Y., Zhou, X. E., Gao, X., He, Y., Liu, W., Ishchenko, A., et al. (2015). Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser. Nature, 523, 561–567.PubMedPubMedCentralCrossRefGoogle Scholar
  97. Kaplan, I. M., Wadia, J. S., & Dowdy, S. F. (2005). Cationic TAT peptide transduction domain enters cells by macropinocytosis. Journal of Controlled Release, 102, 247–253.PubMedCrossRefPubMedCentralGoogle Scholar
  98. Kardinal, C., Posern, G., Zheng, J., Knudsen, B. S., Moarefi, I., & Feller, S. M. (1999). Rational development of cell-penetrating high affinity SH3 domain binding peptides that selectively disrupt the signal transduction of Crk family adapters. Amgen Peptide Technology Group. Annals of the New York Academy of Sciences, 886, 289–292.PubMedCrossRefPubMedCentralGoogle Scholar
  99. Katayama, S., Nakase, I., Yano, Y., Murayama, T., Nakata, Y., Matsuzaki, K., et al. (2013). Effects of pyrenebutyrate on the translocation of arginine-rich cell-penetrating peptides through artificial membranes: Recruiting peptides to the membranes, dissipating liquid-ordered phases, and inducing curvature. Biochimica et Biophysica Acta, 1828, 2134–2142.PubMedCrossRefPubMedCentralGoogle Scholar
  100. Kauffman, W. B., Fuselier, T., He, J., & Wimley, W. C. (2015). Mechanism matters: a taxonomy of cell penetrating peptides. Trends in Biochemical Sciences, 40, 749–764.PubMedPubMedCentralCrossRefGoogle Scholar
  101. Kawaguchi, Y., Takeuchi, T., Kuwata, K., Chiba, J., Hatanaka, Y., Nakase, I., et al. (2016). Syndecan-4 Is a receptor for clathrin-mediated endocytosis of arginine-rich cell-penetrating peptides. Bioconjugate Chemistry, 27, 1119–1130.PubMedCrossRefPubMedCentralGoogle Scholar
  102. Kharrat, N., Belmabrouk, S., Abdelhedi, R., Benmarzoug, R., Assidi, M., Al Qahtani, M. H., et al. (2016). Screening for clusters of charge in human virus proteomes. BMC Genomics, 17, 758.PubMedPubMedCentralCrossRefGoogle Scholar
  103. Kilk, K., Mahlapuu, R., Soomets, U., & Langel, Ü. (2009). Analysis of in vitro toxicity of five cell-penetrating peptides by metabolic profiling. Toxicology, 265, 87–95.PubMedPubMedCentralCrossRefGoogle Scholar
  104. Kim, Y., Kwak, Y., & Chang, R. (2014). Free energy of PAMAM dendrimer adsorption onto model biological membranes. Journal of Physical Chemistry B, 118, 6792–6802.CrossRefGoogle Scholar
  105. Konate, K., Crombez, L., Deshayes, S., Decaffmeyer, M., Thomas, A., Brasseur, R., et al. (2010). Insight into the cellular uptake mechanism of a secondary amphipathic cell-penetrating peptide for siRNA delivery. Biochemistry, 49, 3393–3402.CrossRefGoogle Scholar
  106. Koren, E., & Torchilin, V. P. (2012). Cell-penetrating peptides: Breaking through to the other side. Trends in Molecular Medicine, 18, 385–393.PubMedCrossRefPubMedCentralGoogle Scholar
  107. Kramer, J. R., Schmidt, N. W., Mayle, K. M., Kamei, D. T., Wong, G. C., & Deming, T. J. (2015). Reinventing cell penetrating peptides using glycosylated methionine sulfonium ion sequences. ACS Central Science, 1, 83–88.PubMedPubMedCentralCrossRefGoogle Scholar
  108. Kuo, J. H., Jan, M. S., Lin, Y. L., & Lin, C. (2009). Interactions between octaarginine and U-937 human macrophages: Global gene expression profiling, superoxide anion content, and cytokine production. Journal of Controlled Release, 139, 197–204.PubMedPubMedCentralCrossRefGoogle Scholar
  109. Kurrikoff, K., Gestin, M., & Langel, Ü. (2016). Recent in vivo advances in cell-penetrating peptide-assisted drug delivery. Expert opinion on drug delivery, 13, 373–387.PubMedCrossRefPubMedCentralGoogle Scholar
  110. Lamaziere, A., Burlina, F., Wolf, C., Chassaing, G., Trugnan, G., & Ayala-Sanmartin, J. (2007). Non-metabolic membrane tubulation and permeability induced by bioactive peptides. PLoS ONE, 2, e201.PubMedPubMedCentralCrossRefGoogle Scholar
  111. Lappalainen, T., Sammeth, M., Friedlander, M. R., T Hoen, P. A. C., Monlong, J., Rivas, M. A., et al. (2013). Transcriptome and genome sequencing uncovers functional variation in humans. Nature, 501, 506–511.PubMedPubMedCentralCrossRefGoogle Scholar
  112. Lecher, J. C., Nowak, S. J., & McMurry, J. L. (2017). Breaking in and busting out: Cell-penetrating peptides and the endosomal escape problem. Biomol Concepts, 8, 131–141.PubMedPubMedCentralCrossRefGoogle Scholar
  113. Lee, H. L., Dubikovskaya, E. A., Hwang, H., Semyonov, A. N., Wang, H., Jones, L. R., et al. (2008). Single-molecule motions of oligoarginine transporter conjugates on the plasma membrane of Chinese hamster ovary cells. Journal of the American Chemical Society, 130, 9364–9370.PubMedPubMedCentralCrossRefGoogle Scholar
  114. Lehto, T., Castillo Alvarez, A., Gauck, S., Gait, M. J., Coursindel, T., Wood, M. J., et al. (2014). Cellular trafficking determines the exon skipping activity of Pip6a-PMO in mdx skeletal and cardiac muscle cells. Nucleic Acids Research, 42, 3207–3217.PubMedCrossRefGoogle Scholar
  115. Letoha, T., Keller-Pinter, A., Kusz, E., Kolozsi, C., Bozso, Z., Toth, G., et al. (2010). Cell-penetrating peptide exploited syndecans. Biochimica et Biophysica Acta, 1798, 2258–2265.PubMedCrossRefPubMedCentralGoogle Scholar
  116. Li, B., Lin, L., Lin, H., & Wilson, B. C. (2016). Photosensitized singlet oxygen generation and detection: Recent advances and future perspectives in cancer photodynamic therapy. Journal of Biophotonics, 2, 201600055.Google Scholar
  117. Li, H., Yao, Z., Degenhardt, B., Teper, G., & Papadopoulos, V. (2001). Cholesterol binding at the cholesterol recognition/ interaction amino acid consensus (CRAC) of the peripheral-type benzodiazepine receptor and inhibition of steroidogenesis by an HIV TAT-CRAC peptide. Proceedings of the National Academy of Sciences of the U S A, 98, 1267–1272.CrossRefGoogle Scholar
  118. Li, Z., Zhang, Y., Zhu, D., Li, S., Yu, X., Zhao, Y., et al. (2017). Transporting carriers for intracellular targeting delivery via non-endocytic uptake pathways. Drug Delivery, 24, 45–55.PubMedCrossRefPubMedCentralGoogle Scholar
  119. Libardo, M. D. J., Wang, T. Y., Pellois, J. P., & Angeles-Boza, A. M. (2017). How does membrane oxidation affect cell delivery and cell killing? Trends in Biotechnology, 35, 686–690.PubMedPubMedCentralCrossRefGoogle Scholar
  120. Lindberg, S., Munoz-Alarcon, A., Helmfors, H., Mosqueira, D., Gyllborg, D., Tudoran, O., et al. (2013). PepFect15, a novel endosomolytic cell-penetrating peptide for oligonucleotide delivery via scavenger receptors. International Journal of Pharmaceutics, 441, 242–247.PubMedCrossRefPubMedCentralGoogle Scholar
  121. Lindberg, S., Regberg, J., Eriksson, J., Helmfors, H., Munoz-Alarcon, A., Srimanee, A., et al. (2015). A convergent uptake route for peptide- and polymer-based nucleotide delivery systems. Journal of Controlled Release, 206, 58–66.PubMedCrossRefPubMedCentralGoogle Scholar
  122. Liu, Y., Mei, L., Xu, C., Yu, Q., Shi, K., Zhang, L., et al. (2016). Dual receptor recognizing cell penetrating peptide for selective targeting, efficient intratumoral diffusion and synthesized anti-glioma therapy. Theranostics, 6, 177–191.PubMedPubMedCentralCrossRefGoogle Scholar
  123. Liu, Y., Shoji-Kawata, S., JR Sumpter, R. M., Wei, Y., Ginet, V., Zhang, L., et al. (2013). Autosis is a Na+, K+ -ATPase-regulated form of cell death triggered by autophagy-inducing peptides, starvation, and hypoxia-ischemia. Proceedings of the National Academy of Sciences of the U S A, 110, 20364–20371.CrossRefGoogle Scholar
  124. Lönn, P., & Dowdy, S. F. (2015). Cationic PTD/CPP-mediated macromolecular delivery: Charging into the cell. Expert Opinion on Drug Delivery, 12, 1627–1636.PubMedPubMedCentralCrossRefGoogle Scholar
  125. Lönn, P., Kacsinta, A. D., Cui, X. S., Hamil, A. S., Kaulich, M., Gogoi, K., et al. (2016). Enhancing Endosomal Escape for Intracellular Delivery of Macromolecular Biologic Therapeutics. Sci Rep, 6, 32301.PubMedPubMedCentralCrossRefGoogle Scholar
  126. Lopez-Garcia, B., Gandia, M., Munoz, A., Carmona, L., & Marcos, J. F. (2010). A genomic approach highlights common and diverse effects and determinants of susceptibility on the yeast Saccharomyces cerevisiae exposed to distinct antimicrobial peptides. BMC Microbiology, 10, 289.PubMedPubMedCentralCrossRefGoogle Scholar
  127. Lopez-Garcia, B., Perez-Paya, E., & Marcos, J. F. (2002). Identification of novel hexapeptides bioactive against phytopathogenic fungi through screening of a synthetic peptide combinatorial library. Applied and Environment Microbiology, 68, 2453–2460.CrossRefGoogle Scholar
  128. Lorents, A., Kodavali, P. K., Oskolkov, N., Langel, Ü., Hällbrink, M., & Pooga, M. (2012). Cell-penetrating peptides split into two groups based on modulation of intracellular calcium concentration. Journal of Biological Chemistry, 287, 16880–16889.PubMedPubMedCentralCrossRefGoogle Scholar
  129. Lorieau, J. L., Louis, J. M., & Bax, A. (2013). The impact of influenza hemagglutinin fusion peptide length and viral subtype on its structure and dynamics. Biopolymers, 99, 189–195.PubMedCrossRefPubMedCentralGoogle Scholar
  130. Lowe, R., Shirley, N., Bleackley, M., Dolan, S., & Shafee, T. (2017). Transcriptomics technologies. PLoS Computational Biology, 13, e1005457.PubMedPubMedCentralCrossRefGoogle Scholar
  131. Lundberg, P., el Andaloussi, S., Sutlu, T., Johansson, H., & Langel, Ü. (2007). Delivery of short interfering RNA using endosomolytic cell-penetrating peptides. Faseb J, 21, 2664–2671.PubMedCrossRefPubMedCentralGoogle Scholar
  132. Lundberg, M., & Johansson, M. (2002). Positively charged DNA-binding proteins cause apparent cell membrane translocation. Biochemical and Biophysical Research Communications, 291, 367–371.PubMedCrossRefPubMedCentralGoogle Scholar
  133. Lundberg, P., Magzoub, M., Lindberg, M., Hällbrink, M., Jarvet, J., Eriksson, L. E., et al. (2002). Cell membrane translocation of the N-terminal (1-28) part of the prion protein. Biochemical and Biophysical Research Communications, 299, 85–90.PubMedPubMedCentralCrossRefGoogle Scholar
  134. Lundin, P., Johansson, H., Guterstam, P., Holm, T., Hansen, M., Langel, Ü., et al. (2008). Distinct uptake routes of cell-penetrating peptide conjugates. Bioconjugate Chemistry, 19, 2535–2542.PubMedCrossRefPubMedCentralGoogle Scholar
  135. Ma, G. S., Aznar, N., Kalogriopoulos, N., Midde, K. K., Lopez-Sanchez, I., Sato, E., et al. (2015). Therapeutic effects of cell-permeant peptides that activate G proteins downstream of growth factors. Proceedings of the National Academy of Sciences of the U S A, 112, 29.Google Scholar
  136. Magzoub, M., Sandgren, S., Lundberg, P., Oglecka, K., Lilja, J., Wittrup, A., et al. (2006). N-terminal peptides from unprocessed prion proteins enter cells by macropinocytosis. Biochemical and Biophysical Research Communications, 348, 379–385.PubMedCrossRefPubMedCentralGoogle Scholar
  137. Matsubara, T., Otani, R., Yamashita, M., Maeno, H., Nodono, H., & Sato, T. (2017). Selective intracellular delivery of ganglioside GM3-binding peptide through caveolae/raft-mediated endocytosis. Biomacromolecules, 18, 355–362.PubMedCrossRefPubMedCentralGoogle Scholar
  138. Mayor, S., & Pagano, R. E. (2007). Pathways of clathrin-independent endocytosis. Nature Reviews Molecular Cell Biology, 8, 603–612.PubMedCrossRefPubMedCentralGoogle Scholar
  139. Mckay, M. J., Afrose, F., Koeppe, R. E., 2ND & Greathouse, D. V. (2018). Helix formation and stability in membranes. Biochimica et Biophysica Acta.Google Scholar
  140. Mellert, K., Lamla, M., Scheffzek, K., Wittig, R., & Kaufmann, D. (2012). Enhancing endosomal escape of transduced proteins by photochemical internalisation. PLoS ONE, 7, e52473.PubMedPubMedCentralCrossRefGoogle Scholar
  141. Mellman, I., Fuchs, R., & Helenius, A. (1986). Acidification of the endocytic and exocytic pathways. Annual Review of Biochemistry, 55, 663–700.PubMedCrossRefPubMedCentralGoogle Scholar
  142. Miaczynska, M., Pelkmans, L., & Zerial, M. (2004). Not just a sink: Endosomes in control of signal transduction. Current Opinion in Cell Biology, 16, 400–406.PubMedCrossRefPubMedCentralGoogle Scholar
  143. Mishra, A., Lai, G. H., Schmidt, N. W., Sun, V. Z., Rodriguez, A. R., Tong, R., et al. (2011). Translocation of HIV TAT peptide and analogues induced by multiplexed membrane and cytoskeletal interactions. Proceedings of the National Academy of Sciences of the U S A, 108, 16883–16888.CrossRefGoogle Scholar
  144. Moreira, C., Oliveira, H., Pires, L. R., Simoes, S., Barbosa, M. A., & Pego, A. P. (2009). Improving chitosan-mediated gene transfer by the introduction of intracellular buffering moieties into the chitosan backbone. Acta Biomaterialia, 5, 2995–3006.PubMedCrossRefPubMedCentralGoogle Scholar
  145. Moreno, J. L., Holloway, T., & Gonzalez-Maeso, J. (2013). G protein-coupled receptor heterocomplexes in neuropsychiatric disorders. Prog Mol Biol Transl Sci, 117, 187–205.PubMedPubMedCentralCrossRefGoogle Scholar
  146. Morris, M. C., Deshayes, S., Heitz, F., & Divita, G. (2008). Cell-penetrating peptides: From molecular mechanisms to therapeutics. Biology of the Cell, 100, 201–217.PubMedCrossRefPubMedCentralGoogle Scholar
  147. Mosquera, J., Garcia, I. & Liz-Marzan, L. M. (2018). Cellular uptake of nanoparticles versus small molecules: A matter of size. Accounts of Chemical Research.Google Scholar
  148. Murayama, T., Masuda, T., Afonin, S., Kawano, K., Takatani-Nakase, T., Ida, H., et al. (2017). Loosening of lipid packing promotes oligoarginine entry into cells. Angewandte Chemie (International ed. in English), 56, 7644–7647.CrossRefGoogle Scholar
  149. Murayama, T., Pujals, S., Hirose, H., Nakase, I., & Futaki, S. (2016). Effect of amino acid substitution in the hydrophobic face of amphiphilic peptides on membrane curvature and perturbation: N-terminal helix derived from adenovirus internal protein VI as a model. Biopolymers, 106, 430–439.PubMedCrossRefPubMedCentralGoogle Scholar
  150. Najjar, K., Erazo-Oliveras, A., Brock, D. J., Wang, T. Y., & Pellois, J. P. (2017). An l- to d-amino acid conversion in an endosomolytic analog of the cell-penetrating peptide TAT influences proteolytic stability, endocytic uptake, and endosomal escape. Journal of Biological Chemistry, 292, 847–861.PubMedCrossRefPubMedCentralGoogle Scholar
  151. Nakase, I., Niwa, M., Takeuchi, T., Sonomura, K., Kawabata, N., Koike, Y., et al. (2004). Cellular uptake of arginine-rich peptides: Roles for macropinocytosis and actin rearrangement. Molecular Therapy, 10, 1011–1022.PubMedCrossRefPubMedCentralGoogle Scholar
  152. Ni, Z., Gong, Y., Dai, X., Ding, W., Wang, B., Gong, H., et al. (2015). AU4S: A novel synthetic peptide to measure the activity of ATG4 in living cells. Autophagy, 11, 403–415.PubMedPubMedCentralCrossRefGoogle Scholar
  153. Niessen, S. & Cravatt, B. F. (2010). Proteomics.Google Scholar
  154. Nunez De Villavicencio-Diaz, T., Ramos Gomez, Y., Oliva Arguelles, B., Fernandez Masso, J. R., Rodriguez-Ulloa, A., Cruz Garcia, Y., et al. (2015). Comparative proteomics analysis of the antitumor effect of CIGB-552 peptide in HT-29 colon adenocarcinoma cells. J Proteomics, 126, 163–171.PubMedCrossRefGoogle Scholar
  155. Ohtsuki, T., Miki, S., Kobayashi, S., Haraguchi, T., Nakata, E., Hirakawa, K., Sumita, K., Watanabe, K. & Okazaki, S. (2015). The molecular mechanism of photochemical internalization of cell penetrating peptide-cargo-photosensitizer conjugates. Sci Rep, 5.Google Scholar
  156. Orange, J. S., & May, M. J. (2008). Cell penetrating peptide inhibitors of nuclear factor-kappa B. Cellular and Molecular Life Sciences, 65, 3564–3591.PubMedCrossRefPubMedCentralGoogle Scholar
  157. Paasonen, L., Sharma, S., Braun, G. B., Kotamraju, V. R., Chung, T. D., She, Z. G., et al. (2016). New p32/gC1qR ligands for targeted tumor drug delivery. ChemBioChem, 17, 570–575.PubMedPubMedCentralCrossRefGoogle Scholar
  158. Pack, D. W., Putnam, D., & Langer, R. (2000). Design of imidazole-containing endosomolytic biopolymers for gene delivery. Biotechnology and Bioengineering, 67, 217–223.PubMedCrossRefGoogle Scholar
  159. Pae, J., Liivamagi, L., Lubenets, D., Arukuusk, P., Langel, U. & Pooga, M. (2016). Glycosaminoglycans are required for translocation of amphipathic cell-penetrating peptides across membranes. Biochimica et Biophysica Acta, 23, 30137-7.Google Scholar
  160. Pae, J., Saalik, P., Liivamagi, L., Lubenets, D., Arukuusk, P., Langel, Ü., et al. (2014). Translocation of cell-penetrating peptides across the plasma membrane is controlled by cholesterol and microenvironment created by membranous proteins. Journal of Controlled Release, 192, 103–113.PubMedCrossRefPubMedCentralGoogle Scholar
  161. Palfy, M., Remenyi, A., & Korcsmaros, T. (2012). Endosomal crosstalk: Meeting points for signaling pathways. Trends in Cell Biology, 22, 447–456.PubMedPubMedCentralCrossRefGoogle Scholar
  162. Palm-Apergi, C., Lorents, A., Padari, K., Pooga, M., & Hällbrink, M. (2009). The membrane repair response masks membrane disturbances caused by cell-penetrating peptide uptake. The FASEB Journal, 23, 214–223.PubMedCrossRefPubMedCentralGoogle Scholar
  163. Pan, R., Xu, W., Ding, Y., Lu, S., & Chen, P. (2016). Uptake mechanism and direct translocation of a new CPP for siRNA delivery. Molecular Pharmaceutics, 23, 23.Google Scholar
  164. Pang, H. B., Braun, G. B. & Ruoslahti, E. (2015). Neuropilin-1 and heparan sulfate proteoglycans cooperate in cellular uptake of nanoparticles functionalized by cationic cell-penetrating peptides. Science Advances, 1.Google Scholar
  165. Paolella, G., Lepretti, M., Martucciello, S., Nanayakkara, M., Auricchio, S., Esposito, C., et al. (2018). The toxic alpha-gliadin peptide 31–43 enters cells without a surface membrane receptor. Cell Biology International, 42, 112–120.PubMedCrossRefPubMedCentralGoogle Scholar
  166. Pärnaste, L., Arukuusk, P., Zagato, E., Braeckmans, K., & Langel, Ü. (2016). Methods to follow intracellular trafficking of cell-penetrating peptides. Journal of Drug Targeting, 24, 508–519.PubMedCrossRefPubMedCentralGoogle Scholar
  167. Pazo, M., Juanes, M., Lostale-Seijo, I. & Montenegro, J. (2018). Oligoalanine helical callipers for cell penetration. Chem Commun (Camb).Google Scholar
  168. Peng, S., Barba-Bon, A., Pan, Y. C., Nau, W. M., Guo, D. S., & Hennig, A. (2017). Phosphorylation-responsive membrane transport of peptides. Angewandte Chemie (International ed. in English), 56, 15742–15745.CrossRefGoogle Scholar
  169. Persson, D., Thoren, P. E., Esbjorner, E. K., Goksor, M., Lincoln, P., & Norden, B. (2004). Vesicle size-dependent translocation of penetratin analogs across lipid membranes. Biochimica et Biophysica Acta, 1665, 142–155.PubMedCrossRefPubMedCentralGoogle Scholar
  170. Persson, D., Thoren, P. E., Herner, M., Lincoln, P., & Norden, B. (2003). Application of a novel analysis to measure the binding of the membrane-translocating peptide penetratin to negatively charged liposomes. Biochemistry, 42, 421–429.PubMedCrossRefPubMedCentralGoogle Scholar
  171. Pincus, M. R., Fenelus, M., Sarafraz-Yazdi, E., Adler, V., Bowne, W., & Michl, J. (2011). Anti-cancer peptides from ras-p21 and p53 proteins. Current Pharmaceutical Design, 17, 2677–2698.PubMedCrossRefPubMedCentralGoogle Scholar
  172. Plank, C., Oberhauser, B., Mechtler, K., Koch, C., & Wagner, E. (1994). The influence of endosome-disruptive peptides on gene transfer using synthetic virus-like gene transfer systems. Journal of Biological Chemistry, 269, 12918–12924.PubMedPubMedCentralGoogle Scholar
  173. Polo, S., & di Fiore, P. P. (2006). Endocytosis conducts the cell signaling orchestra. Cell, 124, 897–900.PubMedCrossRefPubMedCentralGoogle Scholar
  174. Pooga, M., Hällbrink, M., Zorko, M., & Langel, Ü. (1998). Cell penetration by transportan. FASEB Journal, 12, 67–77.PubMedPubMedCentralCrossRefGoogle Scholar
  175. Pooga, M., Kut, C., Kihlmark, M., Hällbrink, M., Fernaeus, S., Raid, R., et al. (2001). Cellular translocation of proteins by transportan. The FASEB Journal, 15, 1451–1453.PubMedPubMedCentralCrossRefGoogle Scholar
  176. Prevette, L. E., Benish, N. C., Schoenecker, A. R., & Braden, K. J. (2015). Cell-penetrating compounds preferentially bind glycosaminoglycans over plasma membrane lipids in a charge density- and stereochemistry-dependent manner. Biophysical Chemistry, 207, 40–50.PubMedCrossRefPubMedCentralGoogle Scholar
  177. Prochiantz, A. (2011). Homeoprotein intercellular transfer, the hidden face of cell-penetrating peptides. Methods in Molecular Biology, 683, 249–257.PubMedCrossRefPubMedCentralGoogle Scholar
  178. Prochiantz, A. (2013). Signaling with homeoprotein transcription factors in development and throughout adulthood. Current Genomics, 14, 361–370.PubMedPubMedCentralCrossRefGoogle Scholar
  179. Prochiantz, A., & di Nardo, A. A. (2015). Homeoprotein signaling in the developing and adult nervous system. Neuron, 85, 911–925.PubMedPubMedCentralCrossRefGoogle Scholar
  180. Qifan, W., Fen, N., Ying, X., Xinwei, F., Jun, D., & Ge, Z. (2016). iRGD-targeted delivery of a pro-apoptotic peptide activated by cathepsin B inhibits tumor growth and metastasis in mice. Tumour Biology, 11, 11.Google Scholar
  181. Quach, K., Larochelle, J., LI, X. H., Rhoades, E. & Schepartz, A. (2017). Unique arginine array improves cytosolic localization of hydrocarbon-stapled peptides. Bioorganic & Medicinal Chemistry.Google Scholar
  182. Räägel, H., Hein, M., Kriiska, A., Säälik, P., Floren, A., Langel, Ü., et al. (2013). Cell-penetrating peptide secures an efficient endosomal escape of an intact cargo upon a brief photo-induction. Cellular and Molecular Life Sciences, 70, 4825–4839.PubMedCrossRefPubMedCentralGoogle Scholar
  183. Rhee, M., & Davis, P. (2006). Mechanism of uptake of C105Y, a novel cell-penetrating peptide. Journal of Biological Chemistry, 281, 1233–1240.CrossRefGoogle Scholar
  184. Richard, J. P., Melikov, K., Brooks, H., Prevot, P., Lebleu, B., & Chernomordik, L. V. (2005). Cellular uptake of unconjugated TAT peptide involves clathrin-dependent endocytosis and heparan sulfate receptors. Journal of Biological Chemistry, 280, 15300–15306.PubMedCrossRefPubMedCentralGoogle Scholar
  185. Richard, J. P., Melikov, K., Vives, E., Ramos, C., Verbeure, B., Gait, M. J., et al. (2003). Cell-penetrating peptides. A reevaluation of the mechanism of cellular uptake. Journal of Biological Chemistry, 278, 585–590.CrossRefGoogle Scholar
  186. Rodriguez-Ulloa, A., Gil, J., Ramos, Y., Hernandez-Alvarez, L., Flores, L., Oliva, B., et al. (2015). Proteomic study to survey the CIGB-552 antitumor effect. BioMed Research International, 124082, 20.Google Scholar
  187. Rosadini, C. V., & Kagan, J. C. (2015). Microbial strategies for antagonizing toll-like-receptor signal transduction. Current Opinion in Immunology, 32, 61–70.PubMedCrossRefGoogle Scholar
  188. Rothbard, J. B., Garlington, S., Lin, Q., Kirschberg, T., Kreider, E., McGrane, P. L., et al. (2000). Conjugation of arginine oligomers to cyclosporin a facilitates topical delivery and inhibition of inflammation. Nature Medicine, 6, 1253–1257.PubMedPubMedCentralCrossRefGoogle Scholar
  189. Rullo, A., & Nitz, M. (2010). Importance of the spatial display of charged residues in heparin-peptide interactions. Biopolymers, 93, 290–298.PubMedCrossRefGoogle Scholar
  190. Rullo, A., Qian, J., & Nitz, M. (2011). Peptide-glycosaminoglycan cluster formation involving cell penetrating peptides. Biopolymers, 95, 722–731.PubMedCrossRefGoogle Scholar
  191. Ruoslahti, E. (2016). Tumor penetrating peptides for improved drug delivery. Advanced Drug Delivery Reviews, 31, 30094-1.Google Scholar
  192. Rydstrom, A., Deshayes, S., Konate, K., Crombez, L., Padari, K., Boukhaddaoui, H., et al. (2011). Direct translocation as major cellular uptake for CADY self-assembling peptide-based nanoparticles. PLoS ONE, 6, e25924.PubMedPubMedCentralCrossRefGoogle Scholar
  193. Saalik, P., Padari, K., Niinep, A., Lorents, A., Hansen, M., Jokitalo, E., et al. (2009). Protein delivery with transportans is mediated by caveolae rather than flotillin-dependent pathways. Bioconjugate Chemistry, 20, 877–887.PubMedCrossRefGoogle Scholar
  194. Sagan, S., Bechara, C. & Burlina, F. (2015). Study of CPP mechanisms by mass spectrometry. Methods in Molecular Biology, 2806-4_7.Google Scholar
  195. Sakai, N., Takeuchi, T., Futaki, S., & Matile, S. (2005). Direct observation of anion-mediated translocation of fluorescent oligoarginine carriers into and across bulk liquid and anionic bilayer membranes. ChemBioChem, 6, 114–122.PubMedCrossRefPubMedCentralGoogle Scholar
  196. Sauder, R., Seelig, J., & Ziegler, A. (2011). Thermodynamics of lipid interactions with cell-penetrating peptides. Methods in Molecular Biology, 683, 129–155.PubMedCrossRefPubMedCentralGoogle Scholar
  197. Schmidt, S., Wallbrecher, R., Van Kuppevelt, T. H. & Brock, R. (2015). Methods to study the role of the glycocalyx in the uptake of cell-penetrating peptides. Methods in Molecular Biology, 2806-4_8.Google Scholar
  198. Selbo, P. K., Weyergang, A., Hogset, A., Norum, O. J., Berstad, M. B., Vikdal, M., et al. (2010). Photochemical internalization provides time- and space-controlled endolysosomal escape of therapeutic molecules. Journal of Controlled Release, 148, 2–12.PubMedCrossRefPubMedCentralGoogle Scholar
  199. Shiraishi, T., & Nielsen, P. E. (2014). Cellular delivery of peptide nucleic acids (PNAs). Methods in Molecular Biology, 1050, 193–205.PubMedCrossRefPubMedCentralGoogle Scholar
  200. Shoji-Kawata, S., Sumpter, R., Leveno, M., Campbell, G. R., Zou, Z., Kinch, L., et al. (2013). Identification of a candidate therapeutic autophagy-inducing peptide. Nature, 494, 201–206.PubMedPubMedCentralCrossRefGoogle Scholar
  201. Sigismund, S., Confalonieri, S., Ciliberto, A., Polo, S., Scita, G., & di Fiore, P. P. (2012). Endocytosis and signaling: Cell logistics shape the eukaryotic cell plan. Physiological Reviews, 92, 273–366.PubMedPubMedCentralCrossRefGoogle Scholar
  202. Simeoni, F., Morris, M. C., Heitz, F., & Divita, G. (2003). Insight into the mechanism of the peptide-based gene delivery system MPG: Implications for delivery of siRNA into mammalian cells. Nucleic Acids Research, 31, 2717–2724.PubMedPubMedCentralCrossRefGoogle Scholar
  203. Sogaard, C. K., Blindheim, A., Rost, L. M., Petrovic, V., Nepal, A., Bachke, S., et al. (2018). “Two hits—one stone’’; increased efficacy of cisplatin-based therapies by targeting PCNA’s role in both DNA repair and cellular signaling. Oncotarget, 9, 32448–32465.PubMedPubMedCentralGoogle Scholar
  204. Srimanee, A., Regberg, J., Hallbrink, M., Vajragupta, O., & Langel, U. (2016). Role of scavenger receptors in peptide-based delivery of plasmid DNA across a blood-brain barrier model. International Journal of Pharmaceutics, 500, 128–135.PubMedCrossRefPubMedCentralGoogle Scholar
  205. Stanzl, E. G., Trantow, B. M., Vargas, J. R., & Wender, P. A. (2013). Fifteen years of cell-penetrating, guanidinium-rich molecular transporters: Basic science, research tools, and clinical applications. Accounts of Chemical Research, 46, 2944–2954.PubMedCrossRefPubMedCentralGoogle Scholar
  206. Stern, S. T., Adiseshaiah, P. P., & Crist, R. M. (2012). Autophagy and lysosomal dysfunction as emerging mechanisms of nanomaterial toxicity. Part Fibre Toxicol, 9, 1743–8977.CrossRefGoogle Scholar
  207. Stewart, M. P., Lorenz, A., Dahlman, J., & Sahay, G. (2016a). Challenges in carrier-mediated intracellular delivery: Moving beyond endosomal barriers. Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology, 8, 465–478.PubMedCrossRefPubMedCentralGoogle Scholar
  208. Stewart, M. P., Sharei, A., Ding, X., Sahay, G., Langer, R., & Jensen, K. F. (2016b). In vitro and ex vivo strategies for intracellular delivery. Nature, 538, 183–192.PubMedCrossRefPubMedCentralGoogle Scholar
  209. Sugahara, K. N., Braun, G. B., de Mendoza, T. H., Kotamraju, V. R., French, R. P., Lowy, A. M., et al. (2015). Tumor-penetrating iRGD peptide inhibits metastasis. Molecular Cancer Therapeutics, 14, 120–128.CrossRefGoogle Scholar
  210. Sugahara, K. N., Teesalu, T., Karmali, P. P., Kotamraju, V. R., Agemy, L., Girard, O. M., et al. (2009). Tissue-penetrating delivery of compounds and nanoparticles into tumors. Cancer Cell, 16, 510–520.PubMedPubMedCentralCrossRefGoogle Scholar
  211. Suzuki, T., Futaki, S., Niwa, M., Tanaka, S., Ueda, K., & Sugiura, Y. (2002). Possible existence of common internalization mechanisms among arginine-rich peptides. Journal of Biological Chemistry, 277, 2437–2443.PubMedPubMedCentralCrossRefGoogle Scholar
  212. Szabo, R., Sebestyen, M., Koczan, G., Orosz, A., Mezo, G., & Hudecz, F. (2017). Cellular uptake mechanism of cationic branched polypeptides with Poly[l-Lys] Backbone. ACS Combinatorial Science, 19, 246–254.PubMedCrossRefPubMedCentralGoogle Scholar
  213. Takechi-haraya, Y., Aki, K., Tohyama, Y., Harano, Y., Kawakami, T., Saito, H. & Okamura, E. (2017). Glycosaminoglycan binding and non-endocytic membrane translocation of cell-permeable octaarginine monitored by real-time in-cell NMR spectroscopy. Pharmaceuticals (Basel), 10.Google Scholar
  214. Takechi-haraya, Y. & Saito, H. (2018). Current understanding of physicochemical mechanisms for cell membrane penetration of arginine-rich cell penetrating peptides: Role of glycosaminoglycan interactions. Current Protein & Peptide Science.Google Scholar
  215. Takeuchi, T., & Futaki, S. (2016). Current understanding of direct translocation of arginine-rich cell-penetrating peptides and its internalization mechanisms. Chemical and Pharmaceutical Bulletinb (Tokyo), 64, 1431–1437.CrossRefGoogle Scholar
  216. Takeuchi, T., Kosuge, M., Tadokoro, A., Sugiura, Y., Nishi, M., Kawata, M., et al. (2006). Direct and rapid cytosolic delivery using cell-penetrating peptides mediated by pyrenebutyrate. ACS Chemical Biology, 1, 299–303.PubMedCrossRefPubMedCentralGoogle Scholar
  217. Tammam, S. N., Azzazy, H. M., & Lamprecht, A. (2016). How successful is nuclear targeting by nanocarriers? Journal of Controlled Release, 229, 140–153.PubMedCrossRefPubMedCentralGoogle Scholar
  218. Tanaka, G., Nakase, I., Fukuda, Y., Masuda, R., Oishi, S., Shimura, K., et al. (2012). CXCR219 stimulates macropinocytosis: Implications for cellular uptake of arginine-rich cell-penetrating peptides and HIV. Chemistry & Biology, 19, 1437–1446.CrossRefGoogle Scholar
  219. Teesalu, T., Sugahara, K. N. & Ruoslahti, E. (2013). Tumor-penetrating peptides. Front Oncol, 3.Google Scholar
  220. Tekirdag, K., & Cuervo, A. M. (2018). Chaperone-mediated autophagy and endosomal microautophagy: Joint by a chaperone. Journal of Biological Chemistry, 293, 5414–5424.PubMedCrossRefPubMedCentralGoogle Scholar
  221. Thome, R., Lopes, S. C., Costa, F. T., & Verinaud, L. (2013). Chloroquine: Modes of action of an undervalued drug. Immunology Letters, 153, 50–57.PubMedCrossRefPubMedCentralGoogle Scholar
  222. Thoren, P. E., Persson, D., Isakson, P., Goksor, M., Onfelt, A., & Norden, B. (2003). Uptake of analogs of penetratin, Tat(48–60) and oligoarginine in live cells. Biochemical and Biophysical Research Communications, 307, 100–107.PubMedCrossRefPubMedCentralGoogle Scholar
  223. Tietz, P. S., Yamazaki, K., & Larusso, N. F. (1990). Time-dependent effects of chloroquine on pH of hepatocyte lysosomes. Biochemical Pharmacology, 40, 1419–1421.PubMedCrossRefPubMedCentralGoogle Scholar
  224. Tiriveedhi, V., & Butko, P. (2007). A fluorescence spectroscopy study on the interactions of the TAT-PTD peptide with model lipid membranes. Biochemistry, 46, 3888–3895.PubMedCrossRefPubMedCentralGoogle Scholar
  225. Tiriveedhi, V., Kitchens, K. M., Nevels, K. J., Ghandehari, H., & Butko, P. (2011). Kinetic analysis of the interaction between poly(amidoamine) dendrimers and model lipid membranes. Biochimica et Biophysica Acta, 1, 209–218.CrossRefGoogle Scholar
  226. Tyagi, M., Rusnati, M., Presta, M., & Giacca, M. (2001). Internalization of HIV-1 tat requires cell surface heparan sulfate proteoglycans. Journal of Biological Chemistry, 276, 3254–3261.PubMedCrossRefPubMedCentralGoogle Scholar
  227. Ueda, Y., Wei, F. Y., Hide, T., Michiue, H., Takayama, K., Kaitsuka, T., et al. (2012). Induction of autophagic cell death of glioma-initiating cells by cell-penetrating D-isomer peptides consisting of Pas and the p53 C-terminus. Biomaterials, 33, 9061–9069.PubMedCrossRefPubMedCentralGoogle Scholar
  228. Vandenbroucke, R. E., de Smedt, S. C., Demeester, J., & Sanders, N. N. (2007). Cellular entry pathway and gene transfer capacity of TAT-modified lipoplexes. Biochimica et Biophysica Acta, 1768, 571–579.PubMedCrossRefPubMedCentralGoogle Scholar
  229. Varkouhi, A. K., Scholte, M., Storm, G., & Haisma, H. J. (2011). Endosomal escape pathways for delivery of biologicals. Journal of Controlled Release, 151, 220–228.PubMedCrossRefPubMedCentralGoogle Scholar
  230. Vasconcelos, L., Lehto, T., Madani, F., Radoi, V., Hallbrink, M., Vukojevic, V., et al. (2018). Simultaneous membrane interaction of amphipathic peptide monomers, self-aggregates and cargo complexes detected by fluorescence correlation spectroscopy. Biochimica et Biophysica Acta, 1860, 491–504.PubMedCrossRefPubMedCentralGoogle Scholar
  231. Vazdar, M., Heyda, J., Mason, P. E., Tesei, G., Allolio, C., Lund, M. & Jungwirth, P. (2018). Arginine “Magic”: Guanidinium like-charge ion pairing from aqueous salts to cell penetrating peptides. Accounts of Chemical Research.Google Scholar
  232. Veiman, K. L., Mäger, I., Ezzat, K., Margus, H., Lehto, T., Langel, K., et al. (2013). PepFect14 peptide vector for efficient gene delivery in cell cultures. Molecular Pharmaceutics, 10, 199–210.CrossRefGoogle Scholar
  233. Veloria, J. R., Li, L., Breen, G. A. M., & Goux, W. J. (2017). Novel Cell model for tauopathy induced by a cell-permeable tau-related peptide. ACS Chem Neurosci, 8, 2734–2745.PubMedCrossRefPubMedCentralGoogle Scholar
  234. Verdurmen, W. P., Bovee-Geurts, P. H., Wadhwani, P., Ulrich, A. S., Hallbrink, M., van Kuppevelt, T. H., et al. (2011). Preferential uptake of L- versus D-amino acid cell-penetrating peptides in a cell type-dependent manner. Chemistry & Biology, 18, 1000–1010.CrossRefGoogle Scholar
  235. Verdurmen, W. P., Thanos, M., Ruttekolk, I. R., Gulbins, E., & Brock, R. (2010). Cationic cell-penetrating peptides induce ceramide formation via acid sphingomyelinase: Implications for uptake. Journal of Controlled Release, 147, 171–179.PubMedCrossRefPubMedCentralGoogle Scholar
  236. Vives, E., Brodin, P., & Lebleu, B. (1997). A truncated HIV-1 Tat protein basic domain rapidly translocates through the plasma membrane and accumulates in the cell nucleus. Journal of Biological Chemistry, 272, 16010–16017.PubMedCrossRefPubMedCentralGoogle Scholar
  237. Wadia, J. S., Stan, R. V., & Dowdy, S. F. (2004). Transducible TAT-HA fusogenic peptide enhances escape of TAT-fusion proteins after lipid raft macropinocytosis. Nature Medicine, 10, 310–315.PubMedCrossRefPubMedCentralGoogle Scholar
  238. Wallbrecher, R., Ackels, T., Olea, R. A., Klein, M. J., Caillon, L., Schiller, J., et al. (2017). Membrane permeation of arginine-rich cell-penetrating peptides independent of transmembrane potential as a function of lipid composition and membrane fluidity. Journal of Controlled Release, 256, 68–78.PubMedCrossRefPubMedCentralGoogle Scholar
  239. Wallbrecher, R., Verdurmen, W. P., Schmidt, S., Bovee-Geurts, P. H., Broecker, F., Reinhardt, A., et al. (2014). The stoichiometry of peptide-heparan sulfate binding as a determinant of uptake efficiency of cell-penetrating peptides. Cellular and Molecular Life Sciences, 71, 2717–2729.PubMedPubMedCentralGoogle Scholar
  240. Walrant, A., Cardon, S., Burlina, F., & Sagan, S. (2017). Membrane Crossing and Membranotropic Activity of Cell-Penetrating Peptides: Dangerous Liaisons? Accounts of Chemical Research, 50, 2968–2975.PubMedCrossRefPubMedCentralGoogle Scholar
  241. Wang, J., Macewan, S. R., & Chilkoti, A. (2017). Quantitative mapping of the spatial distribution of nanoparticles in endo-lysosomes by local pH. Nano Letters, 17, 1226–1232.PubMedPubMedCentralCrossRefGoogle Scholar
  242. Wang, H., Sun, H. Q., Zhu, X., Zhang, L., Albanesi, J., Levine, B., et al. (2015). GABARAPs regulate PI4P-dependent autophagosome: Lysosome fusion. Proceedings of the National Academy of Sciences of the U S A, 112, 7015–7020.CrossRefGoogle Scholar
  243. Wang, H. Y., & Wang, R. F. (2012). Enhancing cancer immunotherapy by intracellular delivery of cell-penetrating peptides and stimulation of pattern-recognition receptor signaling. Advances in Immunology, 114, 151–176.PubMedPubMedCentralCrossRefGoogle Scholar
  244. Welzenbach, J., Neuhoff, C., Heidt, H., Cinar, M. U., Looft, C., Schellander, K., et al. (2016). Integrative analysis of metabolomic, proteomic and genomic data to reveal functional pathways and candidate genes for drip loss in pigs. International Journal of Molecular Sciences, 17, 1426.PubMedCentralCrossRefGoogle Scholar
  245. Wender, P. A., Mitchell, D. J., Pattabiraman, K., Pelkey, E. T., Steinman, L., & Rothbard, J. B. (2000). The design, synthesis, and evaluation of molecules that enable or enhance cellular uptake: Peptoid molecular transporters. Proceedings of the National Academy of Sciences, 97, 13003–13008.CrossRefGoogle Scholar
  246. Wibrand, K., Pai, B., Siripornmongcolchai, T., Bittins, M., Berentsen, B., Ofte, M. L., et al. (2012). MicroRNA regulation of the synaptic plasticity-related gene Arc. PLoS ONE, 7, e41688.PubMedPubMedCentralCrossRefGoogle Scholar
  247. Wittrup, A., Zhang, S. H., ten Dam, G. B., van Kuppevelt, T. H., Bengtson, P., Johansson, M., et al. (2009). ScFv antibody-induced translocation of cell-surface heparan sulfate proteoglycan to endocytic vesicles: Evidence for heparan sulfate epitope specificity and role of both syndecan and glypican. United States: The Journal of Biological Chemistry.CrossRefGoogle Scholar
  248. Xu, Z., Yang, L., Xu, S., Zhang, Z., & Cao, Y. (2015). The receptor proteins: Pivotal roles in selective autophagy. Acta Biochimica et Biophysica Sinica, 47, 571–580.PubMedCrossRefPubMedCentralGoogle Scholar
  249. Yang, S., Coles, D. J., Esposito, A., Mitchell, D. J., Toth, I., & Minchin, R. F. (2009). Cellular uptake of self-assembled cationic peptide-DNA complexes: Multifunctional role of the enhancer chloroquine. Journal of Controlled Release, 135, 159–165.PubMedCrossRefPubMedCentralGoogle Scholar
  250. Yang, J., Tsutsumi, H., Furuta, T., Sakurai, M., & Mihara, H. (2014). Interaction of amphiphilic alpha-helical cell-penetrating peptides with heparan sulfate. Organic & Biomolecular Chemistry, 12, 4673–4681.CrossRefGoogle Scholar
  251. Zhang, P., Covic, L. & Kuliopulos, A. (2015a). Pepducins and other lipidated peptides as mechanistic probes and therapeutics. Methods in Molecular Biology, 2806-4_13.Google Scholar
  252. Zhang, P., Leger, A. J., Baleja, J. D., Rana, R., Corlin, T., Nguyen, N., et al. (2015b). Allosteric activation of a G protein-coupled receptor with cell-penetrating receptor mimetics. Journal of Biological Chemistry, 290, 15785–15798.PubMedCrossRefPubMedCentralGoogle Scholar
  253. Zhao, G. X., Pan, H., Ouyang, D. Y., & He, X. H. (2015). The critical molecular interconnections in regulating apoptosis and autophagy. Annals of Medicine, 47, 305–315.PubMedCrossRefPubMedCentralGoogle Scholar
  254. Zhou, J., & Chau, Y. (2016). Different oligoarginine modifications alter endocytic pathways and subcellular trafficking of polymeric nanoparticles. Biomaterials Science, 4, 1462–1472.PubMedCrossRefPubMedCentralGoogle Scholar
  255. Ziegler, A. (2008). Thermodynamic studies and binding mechanisms of cell-penetrating peptides with lipids and glycosaminoglycans. Advanced Drug Delivery Reviews, 60, 580–597.PubMedPubMedCentralCrossRefGoogle Scholar
  256. Ziegler, A., Blatter, X. L., Seelig, A., & Seelig, J. (2003). Protein transduction domains of HIV-1 and SIV TAT interact with charged lipid vesicles. Binding mechanism and thermodynamic analysis. Biochemistry, 42, 9185–9194.PubMedPubMedCentralGoogle Scholar
  257. Ziegler, A., Nervi, P., Durrenberger, M., & Seelig, J. (2005). The cationic cell-penetrating peptide CPP(TAT) derived from the HIV-1 protein TAT is rapidly transported into living fibroblasts: Optical, biophysical, and metabolic evidence. Biochemistry, 44, 138–148.PubMedPubMedCentralCrossRefGoogle Scholar
  258. Ziegler, A., & Seelig, J. (2004). Interaction of the protein transduction domain of HIV-1 TAT with heparan sulfate: Binding mechanism and thermodynamic parameters. Biophysical Journal, 86, 254–263.PubMedPubMedCentralCrossRefGoogle Scholar
  259. Ziegler, A., & Seelig, J. (2007). High affinity of the cell-penetrating peptide HIV-1 Tat-PTD for DNA. Biochemistry, 46, 8138–8145.PubMedCrossRefPubMedCentralGoogle Scholar
  260. Ziegler, A., & Seelig, J. (2008). Binding and clustering of glycosaminoglycans: A common property of mono- and multivalent cell-penetrating compounds. Biophysical Journal, 94, 2142–2149.PubMedCrossRefPubMedCentralGoogle Scholar
  261. Ziegler, A., & Seelig, J. (2011). Contributions of glycosaminoglycan binding and clustering to the biological uptake of the nonamphipathic cell-penetrating peptide WR9. Biochemistry, 50, 4650–4664.PubMedCrossRefPubMedCentralGoogle Scholar
  262. Ziemienowicz, A., Pepper, J., & Eudes, F. (2015). Applications of CPPs in Genome Modulation of Plants. Methods in Molecular Biology, 1324, 417–434.PubMedCrossRefPubMedCentralGoogle Scholar
  263. Zorko, M., & Langel, Ü. (2005). Cell-penetrating peptides: Mechanism and kinetics of cargo delivery. Advanced Drug Delivery Reviews, 57, 529–545.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Ülo Langel
    • 1
    • 2
  1. 1.Department of Biochemistry and BiophysicsStockholm UniversityStockholmSweden
  2. 2.Institute of TechnologyUniversity of TartuTartuEstonia

Personalised recommendations