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Methods for Structural Studies of CPPs

  • Ülo LangelEmail author
Chapter

Abstract

Additional biophysical studies of CPPs have a very high impact on the studies of their molecular mechanisms, i.e. in the understanding of how the CPPs internalize, alone or with a cargo, how they find their interaction partners or how they work per se.

Keywords

Model membrane Biophysical studies Structure 

References

  1. Abdul Ghani, H., Henriques, S. T., Huang, Y. H., Swedberg, J. E., Schroeder, C. I., & Craik, D. J. (2017). Structural and functional characterization of chimeric cyclotides from the Mobius and trypsin inhibitor subfamilies. Biopolymers, 108, 22927.Google Scholar
  2. Ablan, F. D. O., Spaller, B. L., Abdo, K. I., & Almeida, P. F. (2016). Charge distribution fine-tunes the translocation of alpha-helical amphipathic peptides across membranes. Biophysical Journal, 111, 1738–1749.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Afonin, S., Frey, A., Bayerl, S., Fischer, D., Wadhwani, P., Weinkauf, S., et al. (2006). The cell-penetrating peptide TAT(48-60) induces a non-lamellar phase in DMPC membranes. ChemPhysChem, 7, 2134–2142.PubMedCrossRefPubMedCentralGoogle Scholar
  4. Afonin, S., Kubyshkin, V., Mykhailiuk, P. K., Komarov, I. V., & Ulrich, A. S. (2017). Conformational plasticity of the cell-penetrating peptide sap as revealed by solid-state (19)F-NMR and circular dichroism spectroscopies. The Journal of Physical Chemistry B, 121, 6479–6491.PubMedCrossRefPubMedCentralGoogle Scholar
  5. Ahmad Nasrollahi, S., Taghibiglou, C., Fouladdel, S., Dinarvand, R., Moosavi Movahedi, A. A., Azizi, E., et al. (2013). Physicochemical and biological characterization of pep-1/elastin complexes. Chemical Biology & Drug Design, 82, 189–195.CrossRefGoogle Scholar
  6. Albrizio, S., Giusti, L., D’Errico, G., Esposito, C., Porchia, F., Caliendo, G., et al. (2007). Driving forces in the delivery of penetratin conjugated G protein fragment. Journal of Medicinal Chemistry, 50, 1458–1464.PubMedCrossRefPubMedCentralGoogle Scholar
  7. Alhakamy, N. A., Kaviratna, A., Berkland, C. J., & Dhar, P. (2013). Dynamic measurements of membrane insertion potential of synthetic cell penetrating peptides. Langmuir, 29, 15336–15349.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Almarwani, B., Phambu, E. N., Alexander, C., Nguyen, H. A. T., Phambu, N., & Sunda-Meya, A. (2018). Vesicles mimicking normal and cancer cell membranes exhibit differential responses to the cell-penetrating peptide Pep-1. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1860, 1394–1402.CrossRefGoogle Scholar
  9. Almeida, C., Lamaziere, A., Filleau, A., Corvis, Y., Espeau, P., & Ayala-Sanmartin, J. (2016). Membrane re-arrangements and rippled phase stabilisation by the cell penetrating peptide penetratin. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1858, 2584–2591.CrossRefGoogle Scholar
  10. Alves, I. D., Carre, M., Montero, M. P., Castano, S., Lecomte, S., Marquant, R., et al. (2014). A proapoptotic peptide conjugated to penetratin selectively inhibits tumor cell growth. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1838, 2087–2098.CrossRefGoogle Scholar
  11. Andersson, A., Almqvist, J., Hagn, F., & Maler, L. (2004). Diffusion and dynamics of penetratin in different membrane mimicking media. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1661, 18–25.CrossRefGoogle Scholar
  12. Andersson, A., Danielsson, J., Graslund, A., & Maler, L. (2007). Kinetic models for peptide-induced leakage from vesicles and cells. European Biophysics Journal, 36, 621–635.PubMedCrossRefPubMedCentralGoogle Scholar
  13. Anko, M., Majhenc, J., Kogej, K., Sillard, R., Langel, Ü., Anderluh, G., et al. (2012). Influence of stearyl and trifluoromethylquinoline modifications of the cell penetrating peptide TP10 on its interaction with a lipid membrane. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1818, 915–924.CrossRefGoogle Scholar
  14. Antunes, E., Azoia, N. G., Matama, T., Gomes, A. C., & Cavaco-Paulo, A. (2013). The activity of LE10 peptide on biological membranes using molecular dynamics, in vitro and in vivo studies. Colloids and Surfaces B: Biointerfaces, 106, 240–247.PubMedCrossRefPubMedCentralGoogle Scholar
  15. Arsov, Z., Nemec, M., Schara, M., Johansson, H., Langel, Ü., & Zorko, M. (2008). Cholesterol prevents interaction of the cell-penetrating peptide transportan with model lipid membranes. Journal of Peptide Science, 14, 1303–1308.PubMedCrossRefPubMedCentralGoogle Scholar
  16. 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
  17. Arukuusk, P., Pärnaste, L., Margus, H., Eriksson, N. K., Vasconcelos, L., Padari, K., et al. (2013a). Differential endosomal pathways for radically modified peptide vectors. Bioconjugate Chemistry, 24, 1721–1732.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Arukuusk, P., Pärnaste, L., Oskolkov, N., Copolovici, D. M., Margus, H., Padari, K., et al. (2013b). New generation of efficient peptide-based vectors, NickFects, for the delivery of nucleic acids. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1828, 1365–1373.CrossRefGoogle Scholar
  19. Balayssac, S., Burlina, F., Convert, O., Bolbach, G., Chassaing, G., & Lequin, O. (2006). Comparison of penetratin and other homeodomain-derived cell-penetrating peptides: Interaction in a membrane-mimicking environment and cellular uptake efficiency. Biochemistry, 45, 1408–1420.PubMedCrossRefPubMedCentralGoogle Scholar
  20. Banerjee, P., Pal, S., Kundu, N., Mondal, D., & Sarkar, N. (2018). A cell-penetrating peptide induces the self-reproduction of phospholipid vesicles: Understanding the role of the bilayer rigidity. Chemical Communications (Camb).Google Scholar
  21. Barany-Wallje, E., Andersson, A., Gräslund, A., & Mäler, L. (2004). NMR solution structure and position of transportan in neutral phospholipid bicelles. FEBS Letters, 567, 265–269.PubMedCrossRefPubMedCentralGoogle Scholar
  22. Barany-Wallje, E., Andersson, A., Gräslund, A., & Mäler, L. (2006). Dynamics of transportan in bicelles is surface charge dependent. Journal of Biomolecular NMR, 35, 137–147.PubMedCrossRefPubMedCentralGoogle Scholar
  23. 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
  24. Barany-Wallje, E., Keller, S., Serowy, S., Geibel, S., Pohl, P., Bienert, M., et al. (2005). A critical reassessment of penetratin translocation across lipid membranes. Biophysical Journal, 89, 2513–2521.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 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
  26. Bera, S., Kar, R. K., Mondal, S., Pahan, K., & Bhunia, A. (2016). Structural elucidation of the cell-penetrating penetratin peptide in model membranes at the atomic level: Probing hydrophobic interactions in the blood-brain barrier. Biochemistry, 55, 4982–4996.PubMedPubMedCentralCrossRefGoogle Scholar
  27. Berges, R., Balzeau, J., Takahashi, M., Prevost, C., & Eyer, J. (2012). Structure-function analysis of the glioma targeting NFL-TBS.40-63 peptide corresponding to the tubulin-binding site on the light neurofilament subunit. PLoS One, 7, e49436.Google Scholar
  28. Berlose, J. P., Convert, O., Derossi, D., Brunissen, A., & Chassaing, G. (1996). Conformational and associative behaviours of the third helix of antennapedia homeodomain in membrane-mimetic environments. European Journal of Biochemistry, 242, 372–386.PubMedCrossRefPubMedCentralGoogle Scholar
  29. Bernal, F., Tyler, A. F., Korsmeyer, S. J., Walensky, L. D., & Verdine, G. L. (2007). Reactivation of the p53 tumor suppressor pathway by a stapled p53 peptide. Journal of the American Chemical Society, 129, 2456–2457.PubMedPubMedCentralCrossRefGoogle Scholar
  30. Bertrand, J. R., Malvy, C., Auguste, T., Toth, G. K., Kiss-Ivankovits, O., Illyes, E., et al. (2009). Synthesis and studies on cell-penetrating peptides. Bioconjugate Chemistry, 20, 1307–1314.PubMedCrossRefPubMedCentralGoogle Scholar
  31. Biverståhl, H., Andersson, A., Gräslund, A., & Mäler, L. (2004). NMR solution structure and membrane interaction of the N-terminal sequence (1-30) of the bovine prion protein. Biochemistry, 43, 14940–14947.PubMedCrossRefPubMedCentralGoogle Scholar
  32. Bjorklund, J., Biverstahl, H., Graslund, A., Maler, L., & Brzezinski, P. (2006). Real-time transmembrane translocation of penetratin driven by light-generated proton pumping. Biophysical Journal, 91, 16.CrossRefGoogle Scholar
  33. Bode, S. A., Kruis, I. C., Adams, H. P., Boelens, W. C., Pruijn, G. J., van Hest, J. C., et al. (2017). Coiled-coil-mediated activation of oligoarginine cell-penetrating peptides. ChemBioChem, 18, 185–188.PubMedPubMedCentralCrossRefGoogle Scholar
  34. Bodor, N., Toth-Sarudy, E., Holm, T., Pallagi, I., Vass, E., Buchwald, P., et al. (2007). Novel, cell-penetrating molecular transporters with flexible backbones and permanently charged side-chains. Journal of Pharmacy and Pharmacology, 59, 1065–1076.PubMedPubMedCentralCrossRefGoogle Scholar
  35. Burck, J., Roth, S., Wadhwani, P., Afonin, S., Kanithasen, N., Strandberg, E., et al. (2008). Conformation and membrane orientation of amphiphilic helical peptides by oriented circular dichroism. Biophysical Journal, 95, 3872–3881.PubMedPubMedCentralCrossRefGoogle Scholar
  36. Caesar, C. E., Esbjorner, E. K., Lincoln, P., & Norden, B. (2006). Membrane interactions of cell-penetrating peptides probed by tryptophan fluorescence and dichroism techniques: Correlations of structure to cellular uptake. Biochemistry, 45, 7682–7692.PubMedCrossRefPubMedCentralGoogle Scholar
  37. Chang, Y. S., Graves, B., Guerlavais, V., Tovar, C., Packman, K., To, K. H., et al. (2013). Stapled alpha-helical peptide drug development: A potent dual inhibitor of MDM2 and MDMX for p53-dependent cancer therapy. Proceedings of the National Academy of Sciences USA, 110, 14.Google Scholar
  38. Chen, L., & Frankel, A. D. (1995). A peptide interaction in the major groove of RNA resembles protein interactions in the minor groove of DNA. Proceedings of the National Academy of Sciences U S A, 92, 5077–5081.CrossRefGoogle Scholar
  39. Chen, L., Zhang, Q., Yuan, X., Cao, Y., Yuan, Y., Yin, H., et al. (2017). How charge distribution influences the function of membrane-active peptides: Lytic or cell-penetrating? The International Journal of Biochemistry & Cell Biology, 83, 71–75.CrossRefGoogle Scholar
  40. Chithrani, B. D., & Chan, W. C. (2007). Elucidating the mechanism of cellular uptake and removal of protein-coated gold nanoparticles of different sizes and shapes. Nano Letters, 7, 1542–1550.PubMedCrossRefPubMedCentralGoogle Scholar
  41. Chithrani, B. D., Ghazani, A. A., & Chan, W. C. (2006). Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells. Nano Letters, 6, 662–668.PubMedCrossRefPubMedCentralGoogle Scholar
  42. Ciobanasu, C., Siebrasse, J. P., & Kubitscheck, U. (2010). Cell-penetrating HIV1 TAT peptides can generate pores in model membranes. Biophysical Journal, 99, 153–162.PubMedPubMedCentralCrossRefGoogle Scholar
  43. Cohen-Avrahami, M., Libster, D., Aserin, A., & Garti, N. (2012). Penetratin-induced transdermal delivery from H(II) mesophases of sodium diclofenac. Journal of Controlled Release, 159, 419–428.PubMedCrossRefPubMedCentralGoogle Scholar
  44. Cohen-Avrahami, M., Shames, A. I., Ottaviani, M. F., Aserin, A., & Garti, N. (2014). HIV-TAT enhances the transdermal delivery of NSAID drugs from liquid crystalline mesophases. The Journal of Physical Chemistry B, 118, 6277–6287.PubMedCrossRefPubMedCentralGoogle Scholar
  45. Crombez, L., Aldrian-Herrada, G., Konate, K., Nguyen, Q. N., McMaster, G. K., Brasseur, R., et al. (2009). A new potent secondary amphipathic cell-penetrating peptide for siRNA delivery into mammalian cells. Molecular Therapy, 17, 95–103.CrossRefGoogle Scholar
  46. Czajlik, A., Mesko, E., Penke, B., & Perczel, A. (2002). Investigation of penetratin peptides. Part 1. The environment dependent conformational properties of penetratin and two of its derivatives. Journal of Peptide Science, 8, 151–171.PubMedCrossRefPubMedCentralGoogle Scholar
  47. D’Ursi, A. M., Giusti, L., Albrizio, S., Porchia, F., Esposito, C., Caliendo, G., et al. (2006). A membrane-permeable peptide containing the last 21 residues of the G alpha(s) carboxyl terminus inhibits G(s)-coupled receptor signaling in intact cells: Correlations between peptide structure and biological activity. Molecular Pharmacology, 69, 727–736.PubMedPubMedCentralGoogle Scholar
  48. Danielsson, J., Inomata, K., Murayama, S., Tochio, H., Lang, L., Shirakawa, M., et al. (2013). Pruning the ALS-associated protein SOD1 for in-cell NMR. Journal of the American Chemical Society, 135, 10266–10269.PubMedCrossRefPubMedCentralGoogle Scholar
  49. Delaroche, D., Cantrelle, F. X., Subra, F., van Heijenoort, C., Guittet, E., Jiao, C. Y., et al. (2010). Cell-penetrating peptides with intracellular actin-remodeling activity in malignant fibroblasts. Journal of Biological Chemistry, 285, 7712–7721.PubMedCrossRefPubMedCentralGoogle Scholar
  50. Dennison, S. R., Baker, R. D., Nicholl, I. D., & Phoenix, D. A. (2007). Interactions of cell penetrating peptide Tat with model membranes: A biophysical study. Biochemical and Biophysical Research Communications, 363, 178–182.PubMedCrossRefPubMedCentralGoogle Scholar
  51. Desai, P. R., Cormier, A. R., Shah, P. P., Patlolla, R. R., Paravastu, A. K., & Singh, M. (2014). (31)P solid-state NMR based monitoring of permeation of cell penetrating peptides into skin. European Journal of Pharmaceutics and Biopharmaceutics, 86, 190–199.PubMedCrossRefPubMedCentralGoogle Scholar
  52. Deshayes, S., Gerbal-Chaloin, S., Morris, M. C., Aldrian-Herrada, G., Charnet, P., Divita, G., et al. (2004a). On the mechanism of non-endosomial peptide-mediated cellular delivery of nucleic acids. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1667, 141–147.CrossRefGoogle Scholar
  53. Deshayes, S., Heitz, A., Morris, M. C., Charnet, P., Divita, G., & Heitz, F. (2004b). Insight into the mechanism of internalization of the cell-penetrating carrier peptide Pep-1 through conformational analysis. Biochemistry, 43, 1449–1457.PubMedPubMedCentralCrossRefGoogle Scholar
  54. Deshayes, S., Konate, K., Aldrian, G., Heitz, F., & Divita, G. (2011). Interactions of amphipathic CPPs with model membranes. Methods in Molecular Biology, 683, 41–56.PubMedCrossRefPubMedCentralGoogle Scholar
  55. Deshayes, S., Plenat, T., Aldrian-Herrada, G., Divita, G., le Grimellec, C., & Heitz, F. (2004c). Primary amphipathic cell-penetrating peptides: structural requirements and interactions with model membranes. Biochemistry, 43, 7698–7706.PubMedCrossRefPubMedCentralGoogle Scholar
  56. Ding, B., & Chen, Z. (2012). Molecular interactions between cell penetrating peptide Pep-1 and model cell membranes. The Journal of Physical Chemistry B, 116, 2545–2552.PubMedPubMedCentralCrossRefGoogle Scholar
  57. Drin, G., Cottin, S., Blanc, E., Rees, A. R., & Temsamani, J. (2003). Studies on the internalization mechanism of cationic cell-penetrating peptides. Journal of Biological Chemistry, 278, 31192–31201.PubMedPubMedCentralCrossRefGoogle Scholar
  58. Drin, G., Mazel, M., Clair, P., Mathieu, D., Kaczorek, M., & Temsamani, J. (2001). Physico-chemical requirements for cellular uptake of pAntp peptide. Role of lipid-binding affinity. European Journal of Biochemistry, 268, 1304–1314.PubMedPubMedCentralCrossRefGoogle Scholar
  59. Duchardt, F., Ruttekolk, I. R., Verdurmen, W. P., Lortat-Jacob, H., Burck, J., Hufnagel, H., et al. (2009). A cell-penetrating peptide derived from human lactoferrin with conformation-dependent uptake efficiency. Journal of Biological Chemistry, 284, 36099–36108.PubMedCrossRefPubMedCentralGoogle Scholar
  60. Eggimann, G. A., Buschor, S., Darbre, T., & Reymond, J. L. (2013). Convergent synthesis and cellular uptake of multivalent cell penetrating peptides derived from Tat, Antp, pVEC, TP10 and SAP. Organic & Biomolecular Chemistry, 11, 6717–6733.CrossRefGoogle Scholar
  61. 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 (BBA)-Biomembranes, 1798, 1119–1128.CrossRefGoogle Scholar
  62. El-Andaloussi, S., Järver, P., Johansson, H. J., & Langel, Ü. (2007). Cargo-dependent cytotoxicity and delivery efficacy of cell-penetrating peptides: A comparative study. Biochemical Journal, 407, 285–292.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 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
  64. Fanghanel, S., Wadhwani, P., Strandberg, E., Verdurmen, W. P., Burck, J., Ehni, S., et al. (2014). Structure analysis and conformational transitions of the cell penetrating peptide transportan 10 in the membrane-bound state. PLoS ONE, 9, e99653.PubMedPubMedCentralCrossRefGoogle Scholar
  65. Fawell, S., Seery, J., Daikh, Y., Moore, C., Chen, L. L., Pepinsky, B., et al. (1994). Tat-mediated delivery of heterologous proteins into cells. Proceedings of the National Academy of Sciences USA, 91, 664–668.CrossRefGoogle Scholar
  66. Foged, C., Franzyk, H., Bahrami, S., Frokjaer, S., Jaroszewski, J. W., Nielsen, H. M., et al. (2008). Cellular uptake and membrane-destabilising properties of alpha-peptide/beta-peptoid chimeras: lessons for the design of new cell-penetrating peptides. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1778, 2487–2495.CrossRefGoogle Scholar
  67. Franz, J., Graham, D. J., Schmuser, L., Baio, J. E., Lelle, M., Peneva, K., et al. (2015). Full membrane spanning self-assembled monolayers as model systems for UHV-based studies of cell-penetrating peptides. Biointerphases, 10, 019009.PubMedPubMedCentralCrossRefGoogle Scholar
  68. Freire, J. M., Veiga, A. S., de la Torre, B. G., Andreu, D., & Castanho, M. A. (2013). Quantifying molecular partition of cell-penetrating peptide-cargo supramolecular complexes into lipid membranes: Optimizing peptide-based drug delivery systems. Journal of Peptide Science, 19, 182–189.PubMedCrossRefPubMedCentralGoogle Scholar
  69. Futaki, S., Suzuki, T., Ohashi, W., Yagami, T., Tanaka, S., Ueda, K., et al. (2001). Arginine-rich peptides. An abundant source of membrane-permeable peptides having potential as carriers for intracellular protein delivery. Journal of Biological Chemistry, 276, 5836–5840.PubMedCrossRefPubMedCentralGoogle Scholar
  70. Garibotto, F. M., Garro, A. D., Rodriguez, A. M., Raimondi, M., Zacchino, S. A., Perczel, A., et al. (2011). Penetratin analogues acting as antifungal agents. European Journal of Medicinal Chemistry, 46, 370–377.PubMedCrossRefPubMedCentralGoogle Scholar
  71. Gomez-Monterrey, I., Sala, M., Rusciano, M. R., Monaco, S., Maione, A. S., Iaccarino, G., et al. (2013). Characterization of a selective CaMKII peptide inhibitor. European Journal of Medicinal Chemistry, 62, 425–434.PubMedCrossRefPubMedCentralGoogle Scholar
  72. Goncalves, E., Kitas, E., & Seelig, J. (2005). Binding of oligoarginine to membrane lipids and heparan sulfate: Structural and thermodynamic characterization of a cell-penetrating peptide. Biochemistry, 44, 2692–2702.PubMedCrossRefPubMedCentralGoogle Scholar
  73. Gong, Z., Ikonomova, S. P., & Karlsson, A. J. (2017). Secondary structure of cell-penetrating peptides during interaction with fungal cells. Protein Science.Google Scholar
  74. Gongadze, E., van Rienen, U., & Iglic, A. (2011). Generalized stern models of the electric double layer considering the spatial variation of permittivity and finite size of ions in saturation regime. Cellular & Molecular Biology Letters, 16, 576–594.CrossRefGoogle Scholar
  75. Grage, S. L., Afonin, S., Kara, S., Buth, G., & Ulrich, A. S. (2016). Membrane thinning and thickening induced by membrane-active amphipathic peptides. Frontiers in Cell and Developmental Biology, 4.Google Scholar
  76. Grasso, G., Muscat, S., Rebella, M., Morbiducci, U., Audenino, A., Danani, A., et al. (2018). Cell penetrating peptide modulation of membrane biomechanics by Molecular dynamics. Journal of Biomechanics, 73, 137–144.PubMedCrossRefPubMedCentralGoogle Scholar
  77. Greenfield, N. J. (2006). Analysis of the kinetics of folding of proteins and peptides using circular dichroism. Nature Protocols, 1, 2891–2899.PubMedPubMedCentralCrossRefGoogle Scholar
  78. Gräslund, A., & Mäler, L. (2011). Testing membrane interactions of CPPs. Methods in Molecular Biology, 683, 33–40.PubMedCrossRefPubMedCentralGoogle Scholar
  79. Guidotti, G., Brambilla, L., & Rossi, D. (2017). Cell-penetrating peptides: From basic research to clinics. Trends in Pharmacological Sciences, 38, 406–424.PubMedPubMedCentralCrossRefGoogle Scholar
  80. Gupta, A., Mandal, D., Ahmadibeni, Y., Parang, K., & Bothun, G. (2011). Hydrophobicity drives the cellular uptake of short cationic peptide ligands. European Biophysics Journal, 40, 727–736.PubMedCrossRefPubMedCentralGoogle Scholar
  81. 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 (BBA)-Biomembranes, 1788, 2509–2517.CrossRefGoogle Scholar
  82. Henriques, S. T., & Castanho, M. A. (2004). Consequences of nonlytic membrane perturbation to the translocation of the cell penetrating peptide pep-1 in lipidic vesicles. Biochemistry, 43, 9716–9724.PubMedCrossRefPubMedCentralGoogle Scholar
  83. Henriques, S. T., Costa, J., & Castanho, M. A. (2005). Translocation of beta-galactosidase mediated by the cell-penetrating peptide pep-1 into lipid vesicles and human HeLa cells is driven by membrane electrostatic potential. Biochemistry, 44, 10189–10198.PubMedCrossRefPubMedCentralGoogle Scholar
  84. Henriques, S. T., Melo, M. N., & Castanho, M. A. (2007). How to address CPP and AMP translocation? Methods to detect and quantify peptide internalization in vitro and in vivo (Review). Molecular Membrane Biology, 24, 173–184.PubMedCrossRefPubMedCentralGoogle Scholar
  85. Herbig, M. E., Weller, K. M., & Merkle, H. P. (2007). Reviewing biophysical and cell biological methodologies in cell-penetrating peptide (CPP) research. Critical Reviews™ in Therapeutic Drug Carrier Systems, 24, 203–255.CrossRefGoogle Scholar
  86. Herce, H. D., Garcia, A. E., Litt, J., Kane, R. S., Martin, P., Enrique, N., et al. (2009). Arginine-rich peptides destabilize the plasma membrane, consistent with a pore formation translocation mechanism of cell-penetrating peptides. Biophysical Journal, 97, 1917–1925.PubMedPubMedCentralCrossRefGoogle Scholar
  87. Hilinski, G. J., Kim, Y. W., Hong, J., Kutchukian, P. S., Crenshaw, C. M., Berkovitch, S. S., et al. (2014). Stitched alpha-helical peptides via bis ring-closing metathesis. Journal of the American Chemical Society, 136, 12314–12322.PubMedCrossRefPubMedCentralGoogle Scholar
  88. Hong, M., & Su, Y. (2011). Structure and dynamics of cationic membrane peptides and proteins: Insights from solid-state NMR. Protein Science, 20, 641–655.PubMedPubMedCentralCrossRefGoogle Scholar
  89. Hostachy, S., Swiecicki, J. M., Sandt, C., Delsuc, N., & Policar, C. (2016). Photophysical properties of single core multimodal probe for imaging (SCoMPI) in a membrane model and in cells. Dalton Transactions, 45, 2791–2795.PubMedCrossRefPubMedCentralGoogle Scholar
  90. Hu, Y., Liu, X., Sinha, S. K., & Patel, S. (2014). Translocation thermodynamics of linear and cyclic nonaarginine into model DPPC bilayer via coarse-grained molecular dynamics simulation: Implications of pore formation and nonadditivity. The Journal of Physical Chemistry B, 118, 2670–2682.PubMedPubMedCentralCrossRefGoogle Scholar
  91. Hu, Y., Ou, S., & Patel, S. (2013). Free energetics of arginine permeation into model DMPC lipid bilayers: coupling of effective counterion concentration and lateral bilayer dimensions. The Journal of Physical Chemistry B, 117, 11641–11653.PubMedPubMedCentralCrossRefGoogle Scholar
  92. Hu, Y., & Patel, S. (2015). Structural and thermodynamic insight into spontaneous membrane-translocating peptides across model PC/PG lipid bilayers. The Journal of Membrane Biology, 248, 505–515.PubMedCrossRefPubMedCentralGoogle Scholar
  93. Hu, Y., & Patel, S. (2016). Thermodynamics of cell-penetrating HIV1 TAT peptide insertion into PC/PS/CHOL model bilayers through transmembrane pores: The roles of cholesterol and anionic lipids. Soft Matter, 12, 6716–6727.PubMedCrossRefPubMedCentralGoogle Scholar
  94. Hu, Y., Sinha, S. K., & Patel, S. (2015). Investigating hydrophilic pores in model lipid bilayers using molecular simulations: Correlating bilayer properties with pore-formation thermodynamics. Langmuir, 31, 6615–6631.PubMedPubMedCentralCrossRefGoogle Scholar
  95. Huang, C., & Kalodimos, C. G. (2017). Structures of large protein complexes determined by nuclear magnetic resonance spectroscopy. Annual Review of Biophysics, 17, 070816-033701.Google Scholar
  96. Imani, R., Emami, S. H., & Faghihi, S. (2015). Synthesis and characterization of an octaarginine functionalized graphene oxide nano-carrier for gene delivery applications. Physical Chemistry Chemical Physics, 17, 6328–6339.PubMedCrossRefPubMedCentralGoogle Scholar
  97. Inomata, K., Ohno, A., Tochio, H., Isogai, S., Tenno, T., Nakase, I., et al. (2009). High-resolution multi-dimensional NMR spectroscopy of proteins in human cells. Nature, 458, 106–109.PubMedCrossRefPubMedCentralGoogle Scholar
  98. Islam, M. Z., Alam, J. M., Tamba, Y., Karal, M. A., & Yamazaki, M. (2014). The single GUV method for revealing the functions of antimicrobial, pore-forming toxin, and cell-penetrating peptides or proteins. Physical Chemistry Chemical Physics, 16, 15752–15767.PubMedCrossRefPubMedCentralGoogle Scholar
  99. Jafari, M., Xu, W., Pan, R., Sweeting, C. M., Karunaratne, D. N., & Chen, P. (2014). Serum stability and physicochemical characterization of a novel amphipathic peptide C6M1 for siRNA delivery. PLoS ONE, 9, e97797.PubMedPubMedCentralCrossRefGoogle Scholar
  100. Jiang, W., Kim, B. Y., Rutka, J. T., & Chan, W. C. (2008). Nanoparticle-mediated cellular response is size-dependent. Nature Nanotechnology, 3(3), 145–150.  https://doi.org/10.1038/nnano.2008.30 (Epub 2008 Mar 2).PubMedCrossRefPubMedCentralGoogle Scholar
  101. Jiao, C. Y., Sachon, E., Alves, I. D., Chassaing, G., Bolbach, G., & Sagan, S. (2017). Exploiting benzophenone photoreactivity to probe the phospholipid environment and insertion depth of the cell-penetrating peptide penetratin in model membranes. Angewandte Chemie International Edition, 9, 201703465.Google Scholar
  102. Jing, X., Yang, M., Kasimova, M. R., Malmsten, M., Franzyk, H., Jorgensen, L., et al. (2012). Membrane adsorption and binding, cellular uptake and cytotoxicity of cell-penetrating peptidomimetics with alpha-peptide/beta-peptoid backbone: Effects of hydrogen bonding and alpha-chirality in the beta-peptoid residues. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1818, 2660–2668.CrossRefGoogle Scholar
  103. Joanne, P., Galanth, C., Goasdoue, N., Nicolas, P., Sagan, S., Lavielle, S., et al. (2009). Lipid reorganization induced by membrane-active peptides probed using differential scanning calorimetry. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1788, 1772–1781.CrossRefGoogle Scholar
  104. Jobin, M. L., Blanchet, M., Henry, S., Chaignepain, S., Manigand, C., Castano, S., et al. (2015). The role of tryptophans on the cellular uptake and membrane interaction of arginine-rich cell penetrating peptides. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1848, 593–602.CrossRefGoogle Scholar
  105. Jobin, M. L., Bonnafous, P., Temsamani, H., Dole, F., Grelard, A., Dufourc, E. J., et al. (2013). The enhanced membrane interaction and perturbation of a cell penetrating peptide in the presence of anionic lipids: Toward an understanding of its selectivity for cancer cells. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1828, 1457–1470.CrossRefGoogle Scholar
  106. 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
  107. 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 (BBA)-Biomembranes, 12, 25.Google Scholar
  108. 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 (BBA)-Biomembranes, 1828, 2134–2142.CrossRefGoogle Scholar
  109. Kim, Y. W., Grossmann, T. N., & Verdine, G. L. (2011). Synthesis of all-hydrocarbon stapled alpha-helical peptides by ring-closing olefin metathesis. Nature Protocols, 6, 761–771.PubMedCrossRefPubMedCentralGoogle Scholar
  110. Klostermeier, D., Bayer, P., Kraft, M., Frank, R. W., & Rosch, P. (1997). Spectroscopic investigations of HIV-1 trans-activator and related peptides in aqueous solutions. Biophysical Chemistry, 63, 87–96.PubMedCrossRefPubMedCentralGoogle Scholar
  111. Kolesinska, B., Podwysocka, D. J., Rueping, M. A., Seebach, D., Kamena, F., Walde, P., et al. (2013). Permeation through phospholipid bilayers, skin-cell penetration, plasma stability, and CD spectra of alpha- and beta-oligoproline derivatives. Chemistry & Biodiversity, 10, 1–38.CrossRefGoogle Scholar
  112. Koller, D., & Lohner, K. (2014). The role of spontaneous lipid curvature in the interaction of interfacially active peptides with membranes. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1838, 2250–2259.CrossRefGoogle Scholar
  113. Konate, K., Lindberg, M. F., Vaissiere, A., Jourdan, C., Aldrian, G., Margeat, E., et al. (2016). Optimisation of vectorisation property: A comparative study for a secondary amphipathic peptide. International Journal of Pharmaceutics, 509, 71–84.PubMedCrossRefPubMedCentralGoogle Scholar
  114. Kumar, A., Kuhn, L. T., & Balbach, J. (2019). In-cell NMR: Analysis of protein-small molecule interactions, metabolic processes, and protein phosphorylation. International Journal of Molecular Sciences, 20.Google Scholar
  115. Kwon, B., Waring, A. J., & Hong, M. (2013). A 2H solid-state NMR study of lipid clustering by cationic antimicrobial and cell-penetrating peptides in model bacterial membranes. Biophysical Journal, 105, 2333–2342.PubMedPubMedCentralCrossRefGoogle Scholar
  116. Lamaziere, A., Wolf, C., Lambert, O., Chassaing, G., Trugnan, G., & Ayala-Sanmartin, J. (2008). The homeodomain derived peptide Penetratin induces curvature of fluid membrane domains. PLoS ONE, 3, e1938.PubMedPubMedCentralCrossRefGoogle Scholar
  117. Law, M., Jafari, M., & Chen, P. (2008). Physicochemical characterization of siRNA-peptide complexes. Biotechnology Progress, 24, 957–963.PubMedCrossRefPubMedCentralGoogle Scholar
  118. Lea, E. J., Rich, G. T., & Segrest, J. P. (1975). The effects of the membrane-penetrating polypeptide segment of the human erythrocyte MN-glycoprotein on the permeability of model lipid membranes. Biochimica et Biophysica Acta (BBA)-Biomembranes, 382, 41–50.CrossRefGoogle Scholar
  119. Letoha, T., Gaal, S., Somlai, C., Czajlik, A., Perczel, A., & Penke, B. (2003). Membrane translocation of penetratin and its derivatives in different cell lines. Journal of Molecular Recognition, 16, 272–279.PubMedCrossRefPubMedCentralGoogle Scholar
  120. Li, C., Zhao, J., Cheng, K., Ge, Y., Wu, Q., Ye, Y., et al. (2017). Magnetic resonance spectroscopy as a tool for assessing macromolecular structure and function in living cells. Annual Review of Analytical Chemistry, 9, 061516-045237.Google Scholar
  121. Li, S., Su, Y., Luo, W., & Hong, M. (2010). Water-protein interactions of an arginine-rich membrane peptide in lipid bilayers investigated by solid-state nuclear magnetic resonance spectroscopy. The Journal of Physical Chemistry B, 114, 4063–4069.PubMedPubMedCentralCrossRefGoogle Scholar
  122. Lim, Y. B., Lee, E., & Lee, M. (2007). Cell-penetrating-peptide-coated nanoribbons for intracellular nanocarriers. Angewandte Chemie International Edition, 46, 3475–3478.PubMedCrossRefPubMedCentralGoogle Scholar
  123. Lin, J., & Alexander-Katz, A. (2013). Cell membranes open “doors” for cationic nanoparticles/biomolecules: Insights into uptake kinetics. ACS Nano, 7, 10799–10808.PubMedPubMedCentralCrossRefGoogle Scholar
  124. Lind, J., Gräslund, A., & Mäler, L. (2006). Membrane interactions of dynorphins. Biochemistry, 45, 15931–15940.PubMedCrossRefPubMedCentralGoogle Scholar
  125. Lindberg, M., Biverstahl, H., Graslund, A., & Maler, L. (2003). Structure and positioning comparison of two variants of penetratin in two different membrane mimicking systems by NMR. European Journal of Biochemistry, 270, 3055–3063.PubMedCrossRefPubMedCentralGoogle Scholar
  126. Lindberg, M., & Gräslund, A. (2001). The position of the cell penetrating peptide penetratin in SDS micelles determined by NMR. FEBS Letters, 497, 39–44.PubMedCrossRefPubMedCentralGoogle Scholar
  127. Lindberg, M., Jarvet, J., Langel, Ü., & Gräslund, A. (2001). Secondary structure and position of the cell-penetrating peptide transportan in SDS micelles as determined by NMR. Biochemistry, 40, 3141–3149.PubMedCrossRefPubMedCentralGoogle Scholar
  128. Lorents, A., Saalik, P., Langel, U., & Pooga, M. (2018). Arginine-rich cell-penetrating peptides require nucleolin and cholesterol-poor subdomains for translocation across membranes. Bioconjugate Chemistry.Google Scholar
  129. Loret, E. P., Vives, E., Ho, P. S., Rochat, H., van Rietschoten, J., & Johnson, W. C., Jr. (1991). Activating region of HIV-1 Tat protein: vacuum UV circular dichroism and energy minimization. Biochemistry, 30, 6013–6023.PubMedCrossRefPubMedCentralGoogle Scholar
  130. 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
  131. Ma, P., Yu, H., Zhang, X., Mu, H., Chu, Y., Ni, L., et al. (2017). Increased active tumor targeting by an alphavbeta3-targeting and cell-penetrating bifunctional peptide-mediated dendrimer-based conjugate. Pharmaceutical Research, 34, 121–135.PubMedCrossRefPubMedCentralGoogle Scholar
  132. Macchi, S., Nifosi, R., Signore, G., di Pietro, S., Boccardi, C., D’Autilia, F., et al. (2017). Self-aggregation propensity of the Tat peptide revealed by UV-Vis, NMR and MD analyses. Physical Chemistry Chemical Physics, 19, 23910–23914.PubMedCrossRefPubMedCentralGoogle Scholar
  133. Madani, F., Abdo, R., Lindberg, S., Hirose, H., Futaki, S., Langel, U., et al. (2013a). Modeling the endosomal escape of cell-penetrating peptides using a transmembrane pH gradient. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1828, 1198–1204.CrossRefGoogle Scholar
  134. Madani, F., Abdo, R., Lindberg, S., Hirose, H., Futaki, S., Langel, Ü., et al. (2013b). Modeling the endosomal escape of cell-penetrating peptides using a transmembrane pH gradient. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1828, 1198–1204.CrossRefGoogle Scholar
  135. Madani, F., & Gräslund, A. (2015). Investigating membrane interactions and structures of CPPs. Methods in Molecular Biology, 1324, 73–87.PubMedCrossRefPubMedCentralGoogle Scholar
  136. Madani, F., Lindberg, S., Langel, Ü., Futaki, S., & Gräslund, A. (2011a). Mechanisms of cellular uptake of cell-penetrating peptides. Journal of Biophysics, 2011, 414729.PubMedPubMedCentralCrossRefGoogle Scholar
  137. Madani, F., Peralvarez-Marin, A., & Gräslund, A. (2011b). Liposome model systems to study the endosomal escape of cell-penetrating peptides: Transport across phospholipid membranes induced by a proton gradient. Journal of Drug Delivery, 2011, 897592.PubMedCrossRefPubMedCentralGoogle Scholar
  138. Magzoub, M., Eriksson, L. E., & Graslund, A. (2002). Conformational states of the cell-penetrating peptide penetratin when interacting with phospholipid vesicles: effects of surface charge and peptide concentration. Biochimica Et Biophysica Acta (BBA)-Biomembranes, 1563, 53–63.CrossRefGoogle Scholar
  139. Magzoub, M., Eriksson, L. E., & Graslund, A. (2003). Comparison of the interaction, positioning, structure induction and membrane perturbation of cell-penetrating peptides and non-translocating variants with phospholipid vesicles. Biophysical Chemistry, 103, 271–288.CrossRefGoogle Scholar
  140. Magzoub, M., Kilk, K., Eriksson, L. E., Langel, Ü., & Gräslund, A. (2001). Interaction and structure induction of cell-penetrating peptides in the presence of phospholipid vesicles. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1512, 77–89.CrossRefGoogle Scholar
  141. Magzoub, M., Pramanik, A., & Graslund, A. (2005). Modeling the endosomal escape of cell-penetrating peptides: Transmembrane pH gradient driven translocation across phospholipid bilayers. Biochemistry, 44, 14890–14897.PubMedCrossRefPubMedCentralGoogle Scholar
  142. Maiolo, J. R., Ferrer, M., & Ottinger, E. A. (2005). Effects of cargo molecules on the cellular uptake of arginine-rich cell-penetrating peptides. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1712, 161–172.CrossRefGoogle Scholar
  143. Maler, L. (2012). Solution NMR studies of peptide-lipid interactions in model membranes. Molecular Membrane Biology, 29, 155–176.PubMedCrossRefPubMedCentralGoogle Scholar
  144. Maler, L. (2013). Solution NMR studies of cell-penetrating peptides in model membrane systems. Advanced Drug Delivery Reviews, 65, 1002–1011.PubMedCrossRefPubMedCentralGoogle Scholar
  145. Marbella, L. E., Cho, H. S., & Spence, M. M. (2013). Observing the translocation of a mitochondria-penetrating peptide with solid-state NMR. Biochimica et Biophysica Acta (BBA)-Biomembranes, 8, 6.Google Scholar
  146. Margus, H., Arukuusk, P., Langel, U., & Pooga, M. (2016). Characteristics of cell-penetrating peptide/nucleic acid nanoparticles. Molecular Pharmaceutics, 13, 172–179.CrossRefGoogle Scholar
  147. Marinova, Z., Vukojevic, V., Surcheva, S., Yakovleva, T., Cebers, G., Pasikova, N., et al. (2005). Translocation of dynorphin neuropeptides across the plasma membrane. A putative mechanism of signal transmission. Journal of Biological Chemistry, 280, 26360–26370.CrossRefGoogle Scholar
  148. Marion, D. (2013). An introduction to biological NMR spectroscopy. Molecular and Cellular Proteomics, 12, 3006–3025.PubMedCrossRefPubMedCentralGoogle Scholar
  149. Martinek, T. A., & Fulop, F. (2012). Peptidic foldamers: Ramping up diversity. Chemical Society Reviews, 41, 687–702.PubMedCrossRefPubMedCentralGoogle Scholar
  150. McKeown, A. N., Naro, J. L., Huskins, L. J., & Almeida, P. F. (2011). A thermodynamic approach to the mechanism of cell-penetrating peptides in model membranes. Biochemistry, 50, 654–662.PubMedPubMedCentralCrossRefGoogle Scholar
  151. Metzger, A. U., Bayer, P., Willbold, D., Hoffmann, S., Frank, R. W., Goody, R. S., et al. (1997). The interaction of HIV-1 Tat(32-72) with its target RNA: A fluorescence and nuclear magnetic resonance study. Biochemical and Biophysical Research Communications, 241, 31–36.PubMedCrossRefPubMedCentralGoogle Scholar
  152. Metzger, A. U., Schindler, T., Willbold, D., Kraft, M., Steegborn, C., Volkmann, A., et al. (1996). Structural rearrangements on HIV-1 Tat (32-72) TAR complex formation. FEBS Letters, 384, 255–259.PubMedCrossRefPubMedCentralGoogle Scholar
  153. Miles, A. J., & Wallace, B. A. (2016). Circular dichroism spectroscopy of membrane proteins. Chemical Society Reviews, 45, 4859–4872.PubMedCrossRefGoogle Scholar
  154. Mishra, A., Gordon, V. D., Yang, L., Coridan, R., & Wong, G. C. (2008). HIV TAT forms pores in membranes by inducing saddle-splay curvature: Potential role of bidentate hydrogen bonding. Angewandte Chemie International Edition, 47, 2986–2989.PubMedCrossRefGoogle Scholar
  155. 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 USA, 108, 16883–16888.CrossRefGoogle Scholar
  156. Misiewicz, J., Afonin, S., Grage, S. L., van den Berg, J., Strandberg, E., Wadhwani, P., et al. (2015). Action of the multifunctional peptide BP100 on native biomembranes examined by solid-state NMR. Journal of Biomolecular NMR, 61, 287–298.PubMedCrossRefGoogle Scholar
  157. Moellering, R. E., Cornejo, M., Davis, T. N., del Bianco, C., Aster, J. C., Blacklow, S. C., et al. (2009). Direct inhibition of the NOTCH transcription factor complex. Nature, 462, 182–188.PubMedPubMedCentralCrossRefGoogle Scholar
  158. Moghal, M. M. R., Islam, M. Z., Sharmin, S., Levadnyy, V., Moniruzzaman, M., & Yamazaki, M. (2018). Continuous detection of entry of cell-penetrating peptide transportan 10 into single vesicles. Chemistry and Physics of Lipids, 212, 120–129.PubMedPubMedCentralCrossRefGoogle Scholar
  159. Mujeeb, A., Bishop, K., Peterlin, B. M., Turck, C., Parslow, T. G., & James, T. L. (1994). NMR structure of a biologically active peptide containing the RNA-binding domain of human immunodeficiency virus type 1 Tat. Proceedings of the National Academy of Sciences USA, 91, 8248–8252.CrossRefGoogle Scholar
  160. Ohno, A., Inomata, K., Tochio, H., & Shirakawa, M. (2011). Application of NMR spectroscopy in medicinal chemistry and drug discovery. Current Topics in Medicinal Chemistry, 11, 68–73.PubMedCrossRefGoogle Scholar
  161. Orzaez, M., Mondragon, L., Marzo, I., Sanclimens, G., Messeguer, A., Perez-Paya, E., et al. (2007). Conjugation of a novel Apaf-1 inhibitor to peptide-based cell-membrane transporters: Effective methods to improve inhibition of mitochondria-mediated apoptosis. Peptides, 28, 958–968.PubMedCrossRefGoogle Scholar
  162. Ou, S., Lucas, T. R., Zhong, Y., Bauer, B. A., Hu, Y., & Patel, S. (2013). Free energetics and the role of water in the permeation of methyl guanidinium across the bilayer-water interface: Insights from molecular dynamics simulations using charge equilibration potentials. The Journal of Physical Chemistry B, 117, 3578–3592.PubMedCrossRefGoogle Scholar
  163. 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 (BBA)-Biomembranes, 23, 30137-7.Google Scholar
  164. 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
  165. Paneque, T., Ramírez, A., Casillas, D., Duarte, C., Chinea, G., Espinosa Viñals, C., et al. (2017). Cell penetration and secondary structure of a synthetic peptide with anti-HIV activity.Google Scholar
  166. Persson, D., Thoren, P. E., Esbjorner, E. K., Goksor, M., Lincoln, P., & Norden, B. (2004a). Vesicle size-dependent translocation of penetratin analogs across lipid membranes. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1665, 142–155.CrossRefGoogle Scholar
  167. Persson, D., Thoren, P. E., Lincoln, P., & Norden, B. (2004b). Vesicle membrane interactions of penetratin analogues. Biochemistry, 43, 11045–11055.PubMedCrossRefPubMedCentralGoogle Scholar
  168. Phambu, N., Almarwani, B., Alwadai, A., Phambu, E. N., Faciane, N., Marion, C., et al. (2017). Calorimetric and spectroscopic studies of the effects of the cell penetrating peptide Pep-1 and the antimicrobial peptide Combi-2 on vesicles mimicking Escherichia coli membrane. Langmuir, 33, 12908–12915.PubMedCrossRefPubMedCentralGoogle Scholar
  169. Phan, M. D., Kim, H., Lee, S., Yu, C. J., Moon, B., & Shin, K. (2017). HIV peptide-mediated binding behaviors of nanoparticles on a lipid membrane. Langmuir, 33, 2590–2595.PubMedCrossRefPubMedCentralGoogle Scholar
  170. Poillot, C., Dridi, K., Bichraoui, H., Pecher, J., Alphonse, S., Douzi, B., et al. (2010). D-Maurocalcine, a pharmacologically inert efficient cell-penetrating peptide analogue. Journal of Biological Chemistry, 285, 34168–34180.PubMedCrossRefPubMedCentralGoogle Scholar
  171. Polyansky, A. A., Volynsky, P. E., Arseniev, A. S., & Efremov, R. G. (2009). Adaptation of a membrane-active peptide to heterogeneous environment. I. Structural plasticity of the peptide. The Journal of Physical Chemistry B, 113, 1107–1119.PubMedCrossRefPubMedCentralGoogle Scholar
  172. Pujals, S., Fernandez-Carneado, J., Ludevid, M. D., & Giralt, E. (2008). D-SAP: A new, noncytotoxic, and fully protease resistant cell-penetrating peptide. ChemMedChem, 3, 296–301.CrossRefGoogle Scholar
  173. Pujals, S., Miyamae, H., Afonin, S., Murayama, T., Hirose, H., Nakase, I., et al. (2013). Curvature engineering: Positive membrane curvature induced by epsin N-terminal peptide boosts internalization of octaarginine. ACS Chemical Biology, 8, 1894–1899.PubMedCrossRefGoogle Scholar
  174. 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
  175. Quebatte, G., Kitas, E., & Seelig, J. (2014). riDOM, a cell penetrating peptide. Interaction with phospholipid bilayers. Biochimica Et Biophysica Acta (BBA)-Biomembranes, 1838, 968–977.CrossRefGoogle Scholar
  176. Regberg, J., Srimanee, A., Erlandsson, M., Sillard, R., Dobchev, D. A., Karelson, M., et al. (2014). Rational design of a series of novel amphipathic cell-penetrating peptides. International Journal of Pharmaceutics, 464, 111–116.PubMedPubMedCentralCrossRefGoogle Scholar
  177. Regberg, J., Vasconcelos, L., Madani, F., Langel, Ü., & Hällbrink, M. (2016). pH-responsive PepFect cell-penetrating peptides. International Journal of Pharmaceutics, 501, 32–38.PubMedPubMedCentralCrossRefGoogle Scholar
  178. Rejman, J., Oberle, V., Zuhorn, I. S., & Hoekstra, D. (2004). Size-dependent internalization of particles via the pathways of clathrin- and caveolae-mediated endocytosis. Biochemical Journal, 377, 159–169.PubMedPubMedCentralCrossRefGoogle Scholar
  179. Rennert, R., Wespe, C., Beck-Sickinger, A. G., & Neundorf, I. (2006). Developing novel hCT derived cell-penetrating peptides with improved metabolic stability. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1758, 347–354.CrossRefGoogle Scholar
  180. Robison, A. D., Sun, S., Poyton, M. F., Johnson, G. A., Pellois, J. P., Jungwirth, P., et al. (2016). Polyarginine interacts more strongly and cooperatively than polylysine with phospholipid bilayers. The Journal of Physical Chemistry B, 120, 9287–9296.PubMedPubMedCentralCrossRefGoogle Scholar
  181. Ruzza, P., Calderan, A., Guiotto, A., Osler, A., & Borin, G. (2004). Tat cell-penetrating peptide has the characteristics of a poly(proline) II helix in aqueous solution and in SDS micelles. Journal of Peptide Science, 10, 423–426.PubMedCrossRefPubMedCentralGoogle Scholar
  182. Rydberg, H. A., Carlsson, N., & Norden, B. (2012). Membrane interaction and secondary structure of de novo designed arginine-and tryptophan peptides with dual function. Biochemical and Biophysical Research Communications, 427, 261–265.PubMedCrossRefPubMedCentralGoogle Scholar
  183. Sani, M. A., & Separovic, F. (2016). How membrane-active peptides get into lipid membranes. Accounts of Chemical Research, 49, 1130–1138.PubMedCrossRefPubMedCentralGoogle Scholar
  184. Sauder, R., Seelig, J., & Ziegler, A. (2011). Thermodynamics of lipid interactions with cell-penetrating peptides. Methods in Molecular Biology, 683, 129–155.PubMedCrossRefPubMedCentralGoogle Scholar
  185. Schrank, E., Wagner, G. E., & Zangger, K. (2013). Solution NMR studies on the orientation of membrane-bound peptides and proteins by paramagnetic probes. Molecules, 18, 7407–7435.PubMedPubMedCentralCrossRefGoogle Scholar
  186. Schwarz, G., & Arbuzova, A. (1995). Pore kinetics reflected in the dequenching of a lipid vesicle entrapped fluorescent dye. Biochimica et Biophysica Acta (BBA)-Biomembranes, 4, 51–57.CrossRefGoogle Scholar
  187. Sekhar, A., & Kay, L. E. (2019). An NMR view of protein dynamics in health and disease. Annual Review of Biophysics.Google Scholar
  188. Sharmin, S., Islam, M. Z., Karal, M. A., Alam Shibly, S. U., Dohra, H., & Yamazaki, M. (2016). Effects of lipid composition on the entry of cell-penetrating peptide oligoarginine into single vesicles. Biochemistry, 55, 4154–4165.PubMedCrossRefPubMedCentralGoogle Scholar
  189. Sharonov, A., & Hochstrasser, R. M. (2007). Single-molecule imaging of the association of the cell-penetrating peptide Pep-1 to model membranes. Biochemistry, 46, 7963–7972.PubMedCrossRefPubMedCentralGoogle Scholar
  190. Shaw, J. E., Epand, R. F., Hsu, J. C., Mo, G. C., Epand, R. M., & Yip, C. M. (2008). Cationic peptide-induced remodelling of model membranes: Direct visualization by in situ atomic force microscopy. Journal of Structural Biology, 162, 121–138.PubMedCrossRefPubMedCentralGoogle Scholar
  191. Silhol, M., Tyagi, M., Giacca, M., Lebleu, B., & Vives, E. (2002). Different mechanisms for cellular internalization of the HIV-1 Tat-derived cell penetrating peptide and recombinant proteins fused to Tat. European Journal of Biochemistry, 269, 494–501.PubMedCrossRefPubMedCentralGoogle Scholar
  192. Song, J., Kai, M., Zhang, W., Zhang, J., Liu, L., Zhang, B., et al. (2011). Cellular uptake of transportan 10 and its analogs in live cells: Selectivity and structure-activity relationship studies. Peptides, 32, 1934–1941.CrossRefGoogle Scholar
  193. Spinella, S. A., Nelson, R. B., & Elmore, D. E. (2012). Measuring peptide translocation into large unilamellar vesicles. Journal of Visualized Experiments, e3571.Google Scholar
  194. Stetefeld, J., McKenna, S. A., & Patel, T. R. (2016). Dynamic light scattering: A practical guide and applications in biomedical sciences. Biophysical Reviews, 8, 409–427.PubMedPubMedCentralCrossRefGoogle Scholar
  195. Su, Y., Doherty, T., Waring, A. J., Ruchala, P., & Hong, M. (2009). Roles of arginine and lysine residues in the translocation of a cell-penetrating peptide from (13)C, (31)P, and (19)F solid-state NMR. Biochemistry, 48, 4587–4595.PubMedPubMedCentralCrossRefGoogle Scholar
  196. Su, Y., & Hong, M. (2011). Conformational disorder of membrane peptides investigated from solid-state NMR line widths and line shapes. The Journal of Physical Chemistry B, 115, 10758–10767.PubMedPubMedCentralCrossRefGoogle Scholar
  197. Su, Y., Li, S., & Hong, M. (2013). Cationic membrane peptides: Atomic-level insight of structure-activity relationships from solid-state NMR. Amino Acids, 44, 821–833.PubMedCrossRefPubMedCentralGoogle Scholar
  198. Su, Y., Mani, R., Doherty, T., Waring, A. J., & Hong, M. (2008a). Reversible sheet-turn conformational change of a cell-penetrating peptide in lipid bilayers studied by solid-state NMR. Journal of Molecular Biology, 381, 1133–1144.PubMedPubMedCentralCrossRefGoogle Scholar
  199. Su, Y., Mani, R., & Hong, M. (2008b). Asymmetric insertion of membrane proteins in lipid bilayers by solid-state NMR paramagnetic relaxation enhancement: A cell-penetrating Peptide example. Journal of the American Chemical Society, 130, 8856–8864.PubMedPubMedCentralCrossRefGoogle Scholar
  200. Su, Y., Waring, A. J., Ruchala, P., & Hong, M. (2010). Membrane-bound dynamic structure of an arginine-rich cell-penetrating peptide, the protein transduction domain of HIV TAT, from solid-state NMR. Biochemistry, 49, 6009–6020.PubMedPubMedCentralCrossRefGoogle Scholar
  201. Sugawara, M., Resende, J. M., Moraes, C. M., Marquette, A., Chich, J. F., Metz-Boutigue, M. H., et al. (2010). Membrane structure and interactions of human catestatin by multidimensional solution and solid-state NMR spectroscopy. The FASEB Journal, 24, 1737–1746.PubMedCrossRefPubMedCentralGoogle Scholar
  202. Sun, C., Shen, W. C., Tu, J., & Zaro, J. L. (2014a). Interaction between cell-penetrating peptides and acid-sensitive anionic oligopeptides as a model for the design of targeted drug carriers. Molecular Pharmaceutics, 11, 1583–1590.PubMedPubMedCentralCrossRefGoogle Scholar
  203. Sun, D., Forsman, J., Lund, M., & Woodward, C. E. (2014b). Effect of arginine-rich cell penetrating peptides on membrane pore formation and life-times: A molecular simulation study. Physical Chemistry Chemical Physics, 16, 20785–20795.PubMedCrossRefPubMedCentralGoogle Scholar
  204. Sun, D., Forsman, J., & Woodward, C. E. (2015). Atomistic molecular simulations suggest a kinetic model for membrane translocation by arginine-rich peptides. The Journal of Physical Chemistry B, 119, 14413–14420.PubMedPubMedCentralCrossRefGoogle Scholar
  205. Swiecicki, J. M., Bartsch, A., Tailhades, J., di Pisa, M., Heller, B., Chassaing, G., et al. (2014). The efficacies of cell-penetrating peptides in accumulating in large unilamellar vesicles depend on their ability to form inverted micelles. ChemBioChem, 15, 884–891.PubMedCrossRefPubMedCentralGoogle Scholar
  206. Säälik, P., Niinep, A., Pae, J., Hansen, M., Lubenets, D., Langel, Ü., et al. (2011). Penetration without cells: Membrane translocation of cell-penetrating peptides in the model giant plasma membrane vesicles. Journal of Controlled Release, 153, 117–125.PubMedCrossRefPubMedCentralGoogle Scholar
  207. Takechi-Haraya, Y., Aki, K., Tohyama, Y., Harano, Y., Kawakami, T., Saito, H., et al. (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
  208. Takechi, Y., Tanaka, H., Kitayama, H., Yoshii, H., Tanaka, M., & Saito, H. (2012). Comparative study on the interaction of cell-penetrating polycationic polymers with lipid membranes. Chemistry and Physics of Lipids, 165, 51–58.PubMedCrossRefPubMedCentralGoogle Scholar
  209. Takechi, Y., Yoshii, H., Tanaka, M., Kawakami, T., Aimoto, S., & Saito, H. (2011). Physicochemical mechanism for the enhanced ability of lipid membrane penetration of polyarginine. Langmuir, 27, 7099–7107.PubMedCrossRefPubMedCentralGoogle Scholar
  210. Tanaka, K., Kanazawa, T., Shibata, Y., Suda, Y., Fukuda, T., Takashima, Y., et al. (2010). Development of cell-penetrating peptide-modified MPEG-PCL diblock copolymeric nanoparticles for systemic gene delivery. International Journal of Pharmaceutics, 396, 229–238.PubMedCrossRefPubMedCentralGoogle Scholar
  211. Terrone, D., Sang, S. L., Roudaia, L., & Silvius, J. R. (2003). Penetratin and related cell-penetrating cationic peptides can translocate across lipid bilayers in the presence of a transbilayer potential. Biochemistry, 42, 13787–13799.PubMedCrossRefPubMedCentralGoogle Scholar
  212. Tesei, G., Vazdar, M., Jensen, M. R., Cragnell, C., Mason, P. E., Heyda, J., et al. (2017). Self-association of a highly charged arginine-rich cell-penetrating peptide. Proceedings of the National Academy of Sciences USA, 114, 11428–11433.CrossRefGoogle Scholar
  213. Thoren, P. E., Persson, D., Esbjorner, E. K., Goksor, M., Lincoln, P., & Norden, B. (2004). Membrane binding and translocation of cell-penetrating peptides. Biochemistry, 43, 3471–3489.CrossRefGoogle Scholar
  214. Thoren, P. E., Persson, D., Karlsson, M., & Norden, B. (2000). The antennapedia peptide penetratin translocates across lipid bilayers—The first direct observation. FEBS Letters, 482, 265–268.PubMedCrossRefPubMedCentralGoogle Scholar
  215. Ulmschneider, J. P., & Ulmschneider, M. B. (2018). Molecular dynamics simulations are redefining our view of peptides interacting with biological membranes. Accounts of Chemical Research.Google Scholar
  216. Vasconcelos, L., Madani, F., Arukuusk, P., Pärnaste, L., Gräslund, A., & Langel, Ü. (2014). Effects of cargo molecules on membrane perturbation caused by transportan10 based cell-penetrating peptides. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1838, 3118–3129.CrossRefGoogle Scholar
  217. 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
  218. Via, M. A., Del Popolo, M. G., & Wilke, N. (2018). Negative dipole potentials and carboxylic polar head-groups foster the insertion of cell-penetrating-peptides into lipid monolayers. Langmuir.Google Scholar
  219. Wadhwani, P., Heidenreich, N., Podeyn, B., Burck, J., & Ulrich, A. S. (2017). Antibiotic gold: tethering of antimicrobial peptides to gold nanoparticles maintains conformational flexibility of peptides and improves trypsin susceptibility. Biomaterials Science, 5, 817–827.PubMedCrossRefGoogle Scholar
  220. Wadhwani, P., Reichert, J., Burck, J., & Ulrich, A. S. (2012). Antimicrobial and cell-penetrating peptides induce lipid vesicle fusion by folding and aggregation. European Biophysics Journal, 41, 177–187.PubMedCrossRefPubMedCentralGoogle Scholar
  221. Wadhwani, P., Strandberg, E., van den Berg, J., Mink, C., Burck, J., Ciriello, R. A., et al. (2014). Dynamical structure of the short multifunctional peptide BP100 in membranes. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1838, 940–949.CrossRefGoogle Scholar
  222. Walensky, L. D., Kung, A. L., Escher, I., Malia, T. J., Barbuto, S., Wright, R. D., et al. (2004). Activation of apoptosis in vivo by a hydrocarbon-stapled BH3 helix. Science, 305, 1466–1470.PubMedPubMedCentralCrossRefGoogle Scholar
  223. Walrant, A., Correia, I., Jiao, C. Y., Lequin, O., Bent, E. H., Goasdoue, N., et al. (2011). Different membrane behaviour and cellular uptake of three basic arginine-rich peptides. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1808, 382–393.CrossRefGoogle Scholar
  224. Weinberger, A., Walter, V., Macewan, S. R., Schmatko, T., Muller, P., Schroder, A. P., et al. (2017). Cargo self-assembly rescues affinity of cell-penetrating peptides to lipid membranes. Scientific Reports, 7.Google Scholar
  225. Weller, K., Lauber, S., Lerch, M., Renaud, A., Merkle, H. P., & Zerbe, O. (2005). Biophysical and biological studies of end-group-modified derivatives of Pep-1. Biochemistry, 44, 15799–15811.PubMedCrossRefPubMedCentralGoogle Scholar
  226. Wheaten, S. A., Lakshmanan, A., & Almeida, P. F. (2013). Statistical analysis of peptide-induced graded and all-or-none fluxes in giant vesicles. Biophysical Journal, 105, 432–443.PubMedPubMedCentralCrossRefGoogle Scholar
  227. White, S. H., & Wimley, W. C. (1998). Hydrophobic interactions of peptides with membrane interfaces. Biochimica et Biophysica Acta (BBA)-Reviews on Biomembranes, 10, 339–352.CrossRefGoogle Scholar
  228. Willbold, D., Kruger, U., Frank, R., Rosin-Arbesfeld, R., Gazit, A., Yaniv, A., et al. (1993). Sequence-specific resonance assignments of the 1H-NMR spectra of a synthetic, biologically active EIAV Tat protein. Biochemistry, 32, 8439–8445.PubMedCrossRefPubMedCentralGoogle Scholar
  229. Wimley, W. C., & White, S. H. (2000). Determining the membrane topology of peptides by fluorescence quenching. Biochemistry, 39, 161–170.PubMedCrossRefPubMedCentralGoogle Scholar
  230. Witte, K., Olausson, B. E., Walrant, A., Alves, I. D., & Vogel, A. (2013). Structure and dynamics of the two amphipathic arginine-rich peptides RW9 and RL9 in a lipid environment investigated by solid-state NMR and MD simulations. Biochimica et Biophysica Acta (BBA)-Biomembranes, 2, 824–833.CrossRefGoogle Scholar
  231. Wolf, J., Aisenbrey, C., Harmouche, N., Raya, J., Bertani, P., Voievoda, N., et al. (2017). pH-Dependent membrane interactions of the histidine-rich cell-penetrating peptide LAH4-L1. Biophysical Journal, 113, 1290–1300.PubMedPubMedCentralCrossRefGoogle Scholar
  232. Xie, J., Thapa, R., Reverdatto, S., Burz, D. S., & Shekhtman, A. (2009). Screening of small molecule interactor library by using in-cell NMR spectroscopy (SMILI-NMR). Journal of Medicinal Chemistry, 52, 3516–3522.PubMedPubMedCentralCrossRefGoogle Scholar
  233. Yamada, T., Signorelli, S., Cannistraro, S., Beattie, C. W., & Bizzarri, A. R. (2015). Chirality switching within an anionic cell-penetrating peptide inhibits translocation without affecting preferential entry. Molecular Pharmaceutics, 12, 140–149.PubMedCrossRefPubMedCentralGoogle Scholar
  234. Yamashita, H., Demizu, Y., Shoda, T., Sato, Y., Oba, M., Tanaka, M., et al. (2014). Amphipathic short helix-stabilized peptides with cell-membrane penetrating ability. Bioorganic & Medicinal Chemistry, 22, 2403–2408.CrossRefGoogle Scholar
  235. Yamashita, H., Oba, M., Misawa, T., Tanaka, M., Hattori, T., Naito, M., et al. (2016). A helix-stabilized cell-penetrating peptide as an intracellular delivery tool. ChemBioChem, 17, 137–140.PubMedPubMedCentralCrossRefGoogle Scholar
  236. Yandek, L. E., Pokorny, A., Floren, A., Knoelke, K., Langel, Ü., & Almeida, P. F. (2007). Mechanism of the cell-penetrating peptide transportan 10 permeation of lipid bilayers. Biophysical Journal, 92, 2434–2444.PubMedPubMedCentralCrossRefGoogle Scholar
  237. 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
  238. Zamora-Carreras, H., Strandberg, E., Muhlhauser, P., Burck, J., Wadhwani, P., Jimenez, M. A., et al. (2016). Alanine scan and (2)H NMR analysis of the membrane-active peptide BP100 point to a distinct carpet mechanism of action. Biochimica et Biophysica Acta (BBA)-Biomembranes, 6, 11.Google Scholar
  239. Zamotaiev, O. M., Postupalenko, V. Y., Shvadchak, V. V., Pivovarenko, V. G., Klymchenko, A. S., & Mely, Y. (2014). Monitoring penetratin interactions with lipid membranes and cell internalization using a new hydration-sensitive fluorescent probe. Organic & Biomolecular Chemistry, 12, 7036–7044.CrossRefGoogle Scholar
  240. Zhang, H., Curreli, F., Waheed, A. A., Mercredi, P. Y., Mehta, M., Bhargava, P., et al. (2013). Dual-acting stapled peptides target both HIV-1 entry and assembly. Retrovirology, 10, 136.PubMedPubMedCentralCrossRefGoogle Scholar
  241. Zhang, H., Zhao, Q., Bhattacharya, S., Waheed, A. A., Tong, X., Hong, A., et al. (2008). A cell-penetrating helical peptide as a potential HIV-1 inhibitor. Journal of Molecular Biology, 378, 565–580.PubMedPubMedCentralCrossRefGoogle Scholar
  242. Zhu, W. L., Hahm, K. S., & Shin, S. Y. (2009). Cell selectivity and mechanism of action of short antimicrobial peptides designed from the cell-penetrating peptide Pep-1. Journal of Peptide Science, 15, 569–575.PubMedCrossRefPubMedCentralGoogle Scholar
  243. Zhu, W. L., & Shin, S. Y. (2009). Antimicrobial and cytolytic activities and plausible mode of bactericidal action of the cell penetrating peptide penetratin and its lys-linked two-stranded peptide. Chemical Biology & Drug Design, 73, 209–215.CrossRefGoogle Scholar
  244. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  245. 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

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© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

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

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