Skip to main content
SpringerLink
Log in

Classes of Cell-Penetrating Peptides

  • Protocol
Cell-Penetrating Peptides

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1324))

Abstract

During the three decades of cell-penetrating peptides era the superfamily of CPPs has rapidly expanded, and the quest for new sequences continues. CPPs have been well recognized by scientific community and they have been used for transduction of a wide variety of molecules and particles into cultured cells and in vivo. In parallel with application of CPPs for delivering of active payloads, the mechanisms that such peptides take advantage of for gaining access to cells’ insides have been in the focus of intense studies. Although the common denominator “cell penetration” unites all CPPs, the interaction partners on the cell surface, evoked cellular responses and even the uptake mechanisms might greatly vary between different peptide types. Here we present some possibilities for classification of CPPs based on their type of origin, physical-chemical properties, and the extent of modifications and design efforts. We also briefly analyze the internalization mechanisms with regard to their classification into groups based on physical-chemical characteristics.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Frankel AD, Pabo CO (1988) Cellular uptake of the tat protein from human immunodeficiency virus. Cell 55:1189–1193

    Article  CAS  PubMed  Google Scholar 

  2. Green M, Loewenstein PM (1988) Autonomous functional domains of chemically synthesized human immunodeficiency virus tat trans-activator protein. Cell 55:1179–1188

    Article  CAS  PubMed  Google Scholar 

  3. Joliot A, Pernelle C, Deagostini-Bazin H et al (1991) Antennapedia homeobox peptide regulates neural morphogenesis. Proc Natl Acad Sci U S A 88:1864–1868

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Derossi D, Joliot AH, Chassaing G et al (1994) The third helix of the Antennapedia homeodomain translocates through biological membranes. J Biol Chem 269:10444–10450

    CAS  PubMed  Google Scholar 

  5. Derossi D, Calvet S, Trembleau A et al (1996) Cell internalization of the third helix of the Antennapedia homeodomain is receptor-independent. J Biol Chem 271:18188–18193

    Article  CAS  PubMed  Google Scholar 

  6. Derossi D, Chassaing G, Prochiantz A (1998) Trojan peptides: the penetratin system for intracellular delivery. Trends Cell Biol 8:84–87

    Article  CAS  PubMed  Google Scholar 

  7. Lee SH, Castagner B, Leroux JC (2013) Is there a future for cell-penetrating peptides in oligonucleotide delivery? Eur J Pharm Biopharm 85:5–11

    Article  CAS  PubMed  Google Scholar 

  8. Abes R, Arzumanov AA, Moulton HM et al (2007) Cell-penetrating-peptide-based delivery of oligonucleotides: an overview. Biochem Soc Trans 35:775–779

    Article  CAS  PubMed  Google Scholar 

  9. Cerrato CP, Lehto T, Langel Ü (2014) Peptide-based vectors: recent developments. Biomol Concepts 5:479–488

    Article  CAS  PubMed  Google Scholar 

  10. Vasconcelos L, Parn K, Langel Ü (2013) Therapeutic potential of cell-penetrating peptides. Ther Deliv 4:573–591

    Article  CAS  PubMed  Google Scholar 

  11. Brock R (2014) The uptake of arginine-rich cell-penetrating peptides: putting the puzzle together. Bioconjug Chem 25:863–868

    Article  CAS  PubMed  Google Scholar 

  12. Wang F, Wang Y, Zhang X et al (2014) Recent progress of cell-penetrating peptides as new carriers for intracellular cargo delivery. J Control Release 174:126–136

    Article  CAS  PubMed  Google Scholar 

  13. Copolovici DM, Langel K, Eriste E et al (2014) Cell-penetrating peptides: design, synthesis, and applications. ACS Nano 8:1972–1994

    Article  CAS  PubMed  Google Scholar 

  14. Shi NQ, Qi XR, Xiang B et al (2014) A survey on “Trojan Horse” peptides: opportunities, issues and controlled entry to “Troy”. J Control Release 194C:53–70

    Article  CAS  Google Scholar 

  15. Margus H, Padari K, Pooga M (2012) Cell-penetrating peptides as versatile vehicles for oligonucleotide delivery. Mol Ther 20:525–533

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Fu A, Tang R, Hardie J et al (2014) Promises and pitfalls of intracellular delivery of proteins. Bioconjug Chem 25:1602–1608

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Margus H, Padari K, Pooga M (2013) Insights into cell entry and intracellular trafficking of peptide and protein drugs provided by electron microscopy. Adv Drug Deliv Rev 65:1031–1038

    Article  CAS  PubMed  Google Scholar 

  18. Liu E, Sheng J, Ye J et al (2014) CPP mediated insulin delivery: current status and promising future. Curr Pharm Biotechnol 15:240–255

    Article  CAS  PubMed  Google Scholar 

  19. Metildi CA, Felsen CN, Savariar EN et al (2015) Ratiometric activatable cell-penetrating peptides label pancreatic cancer, enabling fluorescence-guided surgery, which reduces metastases and recurrence in orthotopic mouse models. Ann Surg Oncol 22:2082–2087

    Google Scholar 

  20. Nguyen QT, Tsien RY (2013) Fluorescence-guided surgery with live molecular navigation – a new cutting edge. Nat Rev Cancer 13:653–662

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Olson ES, Jiang T, Aguilera TA et al (2010) Activatable cell penetrating peptides linked to nanoparticles as dual probes for in vivo fluorescence and MR imaging of proteases. Proc Natl Acad Sci U S A 107:4311–4316

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Jiang T, Olson ES, Nguyen QT et al (2004) Tumor imaging by means of proteolytic activation of cell-penetrating peptides. Proc Natl Acad Sci U S A 101:17867–17872

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Koren E, Torchilin VP (2012) Cell-penetrating peptides: breaking through to the other side. Trends Mol Med 18:385–393

    Article  CAS  PubMed  Google Scholar 

  24. Torchilin VP (2008) Cell penetrating peptide-modified pharmaceutical nanocarriers for intracellular drug and gene delivery. Biopolymers 90:604–610

    Article  CAS  PubMed  Google Scholar 

  25. Andreev OA, Engelman DM, Reshetnyak YK (2010) pH-sensitive membrane peptides (pHLIPs) as a novel class of delivery agents. Mol Membr Biol 27:341–352

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Chen B, Friedman B, Whitney MA et al (2012) Thrombin activity associated with neuronal damage during acute focal ischemia. J Neurosci 32:7622–7631

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Zhang L, Hoffman JA, Ruoslahti E (2005) Molecular profiling of heart endothelial cells. Circulation 112:1601–1611

    Article  CAS  PubMed  Google Scholar 

  28. Teesalu T, Sugahara KN, Ruoslahti E (2012) Mapping of vascular ZIP codes by phage display. Methods Enzymol 503:35–56

    Article  CAS  PubMed  Google Scholar 

  29. Ruoslahti E (2000) Targeting tumor vasculature with homing peptides from phage display. Semin Cancer Biol 10:435–442

    Article  CAS  PubMed  Google Scholar 

  30. Chaloin L, Vidal P, Heitz A et al (1997) Conformations of primary amphipathic carrier peptides in membrane mimicking environments. Biochemistry 36:11179–11187

    Article  CAS  PubMed  Google Scholar 

  31. Morris MC, Depollier J, Mery J et al (2001) A peptide carrier for the delivery of biologically active proteins into mammalian cells. Nat Biotechnol 19:1173–1176

    Article  CAS  PubMed  Google Scholar 

  32. Stewart KM, Horton KL, Kelley SO (2008) Cell-penetrating peptides as delivery vehicles for biology and medicine. Org Biomol Chem 6:2242–2255

    Article  CAS  PubMed  Google Scholar 

  33. Shaheen SM, Akita H, Nakamura T et al (2011) KALA-modified multi-layered nanoparticles as gene carriers for MHC class-I mediated antigen presentation for a DNA vaccine. Biomaterials 32:6342–6350

    Article  CAS  PubMed  Google Scholar 

  34. Milletti F (2012) Cell-penetrating peptides: classes, origin, and current landscape. Drug Discov Today 17:850–860

    Article  CAS  PubMed  Google Scholar 

  35. Reissmann S (2014) Cell penetration: scope and limitations by the application of cell-penetrating peptides. J Pept Sci 20:760–784

    Article  CAS  PubMed  Google Scholar 

  36. Lindgren M, Hällbrink M, Prochiantz A et al (2000) Cell-penetrating peptides. Trends Pharmacol Sci 21:99–103

    Article  CAS  PubMed  Google Scholar 

  37. Prochiantz A (2000) Messenger proteins: homeoproteins, TAT and others. Curr Opin Cell Biol 12:400–406

    Article  CAS  PubMed  Google Scholar 

  38. 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. J Biol Chem 272:16010–16017

    Article  CAS  PubMed  Google Scholar 

  39. Schwarze SR, Ho A, Vocero-Akbani A et al (1999) In vivo protein transduction: delivery of a biologically active protein into the mouse. Science 285:1569–1572

    Article  CAS  PubMed  Google Scholar 

  40. Derossi D, Prochiantz A (1995) Internalization of macromolecules by live cells. Restor Neurol Neurosci 8:7–10

    CAS  PubMed  Google Scholar 

  41. Langel Ü (2002) Cell-penetrating peptides, processes and applications. CRC Press, Boca Raton, FL

    Google Scholar 

  42. Elmquist A, Lindgren M, Bartfai T et al (2001) VE-cadherin-derived cell-penetrating peptide, pVEC, with carrier functions. Exp Cell Res 269:237–244

    Article  CAS  PubMed  Google Scholar 

  43. Elliott G, O’Hare P (1997) Intercellular trafficking and protein delivery by a herpesvirus structural protein. Cell 88:223–233

    Article  CAS  PubMed  Google Scholar 

  44. Futaki S, Suzuki T, Ohashi W et al (2001) Arginine-rich peptides. An abundant source of membrane-permeable peptides having potential as carriers for intracellular protein delivery. J Biol Chem 276:5836–5840

    Article  CAS  PubMed  Google Scholar 

  45. Kilk K, Magzoub M, Pooga M et al (2001) Cellular internalization of a cargo complex with a novel peptide derived from the third helix of the islet-1 homeodomain. comparison with the penetratin peptide. Bioconjug Chem 12:911–916

    Article  CAS  PubMed  Google Scholar 

  46. Balayssac S, Burlina F, Convert O et al (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

    Article  CAS  PubMed  Google Scholar 

  47. Han K, Jeon MJ, Kim KA et al (2000) Efficient intracellular delivery of GFP by homeodomains of Drosophila Fushi-tarazu and Engrailed proteins. Mol Cells 10:728–732

    Article  CAS  PubMed  Google Scholar 

  48. Machova Z, Muhle C, Krauss U et al (2002) Cellular internalization of enhanced green fluorescent protein ligated to a human calcitonin-based carrier peptide. Chembiochem 3:672–677

    Article  CAS  PubMed  Google Scholar 

  49. Rennert R, Neundorf I, Beck-Sickinger AG (2008) Calcitonin-derived peptide carriers: mechanisms and application. Adv Drug Deliv Rev 60:485–498

    Article  CAS  PubMed  Google Scholar 

  50. Duchardt F, Ruttekolk IR, Verdurmen WP et al (2009) A cell-penetrating peptide derived from human lactoferrin with conformation-dependent uptake efficiency. J Biol Chem 284:36099–36108

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  51. Radis-Baptista G, Kerkis I (2011) Crotamine, a small basic polypeptide myotoxin from rattlesnake venom with cell-penetrating properties. Curr Pharm Des 17:4351–4361

    Article  CAS  PubMed  Google Scholar 

  52. Esteve E, Mabrouk K, Dupuis A et al (2005) Transduction of the scorpion toxin maurocalcine into cells. Evidence that the toxin crosses the plasma membrane. J Biol Chem 280:12833–12839

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  53. Tisseyre C, Bahembera E, Dardevet L et al (2013) Cell penetration properties of a highly efficient mini maurocalcine Peptide. Pharmaceuticals (Basel) 6:320–339

    Article  CAS  Google Scholar 

  54. Pooga M, Hällbrink M, Zorko M et al (1998) Cell penetration by transportan. FASEB J 12:67–77

    CAS  PubMed  Google Scholar 

  55. Morris MC, Vidal P, Chaloin L et al (1997) A new peptide vector for efficient delivery of oligonucleotides into mammalian cells. Nucleic Acids Res 25:2730–2736

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  56. Crombez L, Aldrian-Herrada G, Konate K et al (2009) A new potent secondary amphipathic cell-penetrating peptide for siRNA delivery into mammalian cells. Mol Ther 17:95–103

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  57. Ivanova GD, Arzumanov A, Abes R et al (2008) Improved cell-penetrating peptide-PNA conjugates for splicing redirection in HeLa cells and exon skipping in mdx mouse muscle. Nucleic Acids Res 36:6418–6428

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  58. Repke H, Bienert M (1987) Mast cell activation – a receptor-independent mode of substance P action? FEBS Lett 221:236–240

    Article  CAS  PubMed  Google Scholar 

  59. Oehlke J, Beyermann M, Wiesner B et al (1997) Evidence for extensive and non-specific translocation of oligopeptides across plasma membranes of mammalian cells. Biochim Biophys Acta 1330:50–60

    Article  CAS  PubMed  Google Scholar 

  60. Scheller A, Wiesner B, Melzig M et al (2000) Evidence for an amphipathicity independent cellular uptake of amphipathic cell-penetrating peptides. Eur J Biochem 267:6043–6050

    Article  CAS  PubMed  Google Scholar 

  61. Mitchell DJ, Kim DT, Steinman L et al (2000) Polyarginine enters cells more efficiently than other polycationic homopolymers. J Pept Res 56:318–325

    Article  CAS  PubMed  Google Scholar 

  62. Futaki S (2006) Oligoarginine vectors for intracellular delivery: design and cellular-uptake mechanisms. Biopolymers 84:241–249

    Article  CAS  PubMed  Google Scholar 

  63. Sugiyama S, Di Nardo AA, Aizawa S et al (2008) Experience-dependent transfer of Otx2 homeoprotein into the visual cortex activates postnatal plasticity. Cell 134:508–520

    Article  CAS  PubMed  Google Scholar 

  64. Wizenmann A, Brunet I, Lam JS et al (2009) Extracellular Engrailed participates in the topographic guidance of retinal axons in vivo. Neuron 64:355–366

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  65. Metkar SS, Marchioretto M, Antonini V et al (2015) Perforin oligomers form arcs in cellular membranes: a locus for intracellular delivery of granzymes. Cell Death Differ 22:74

    Google Scholar 

  66. Ziegler A (2008) Thermodynamic studies and binding mechanisms of cell-penetrating peptides with lipids and glycosaminoglycans. Adv Drug Deliv Rev 60:580–597

    Article  CAS  PubMed  Google Scholar 

  67. Madani F, Lindberg S, Langel Ü et al (2011) Mechanisms of cellular uptake of cell-penetrating peptides. J Biophys 2011:414729

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  68. Tünnemann G, Martin RM, Haupt S et al (2006) Cargo-dependent mode of uptake and bioavailability of TAT-containing proteins and peptides in living cells. FASEB J 20:1775–1784

    Article  PubMed  CAS  Google Scholar 

  69. Verdurmen WP, Brock R (2011) Biological responses towards cationic peptides and drug carriers. Trends Pharmacol Sci 32:116–124

    Article  CAS  PubMed  Google Scholar 

  70. Nakase I, Hirose H, Tanaka G et al (2009) Cell-surface accumulation of flock house virus-derived peptide leads to efficient internalization via macropinocytosis. Mol Ther 17:1868–1876

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  71. De Coupade C, Fittipaldi A, Chagnas V et al (2005) Novel human-derived cell-penetrating peptides for specific subcellular delivery of therapeutic biomolecules. Biochem J 390:407–418

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  72. Reynolds F, Weissleder R, Josephson L (2005) Protamine as an efficient membrane-translocating peptide. Bioconjug Chem 16:1240–1245

    Article  CAS  PubMed  Google Scholar 

  73. Rosenbluh J, Hariton-Gazal E, Dagan A et al (2005) Translocation of histone proteins across lipid bilayers and Mycoplasma membranes. J Mol Biol 345:387–400

    Article  CAS  PubMed  Google Scholar 

  74. Joliot A (2005) Transduction peptides within naturally occurring proteins. Sci STKE 2005:pe54

    PubMed  Google Scholar 

  75. Christiaens B, Symoens S, Verheyden S et al (2002) Tryptophan fluorescence study of the interaction of penetratin peptides with model membranes. Eur J Biochem 269:2918–2926

    Article  CAS  PubMed  Google Scholar 

  76. Drin G, Mazel M, Clair P et al (2001) Physico-chemical requirements for cellular uptake of pAntp peptide. Role of lipid-binding affinity. Eur J Biochem 268:1304–1314

    Article  CAS  PubMed  Google Scholar 

  77. Bechara C, Pallerla M, Burlina F et al (2015) Massive glycosaminoglycan-dependent entry of Trp-containing cell-penetrating peptides induced by exogenous sphingomyelinase or cholesterol depletion. Cell Mol Life Sci 72:809

    Google Scholar 

  78. Thoren PE, Persson D, Esbjorner EK et al (2004) Membrane binding and translocation of cell-penetrating peptides. Biochemistry 43:3471–3489

    Article  CAS  PubMed  Google Scholar 

  79. Konate K, Crombez L, Deshayes S et al (2010) Insight into the cellular uptake mechanism of a secondary amphipathic cell-penetrating peptide for siRNA delivery. Biochemistry 49:3393–3402

    Article  CAS  PubMed  Google Scholar 

  80. Hariton-Gazal E, Feder R, Mor A et al (2002) Targeting of nonkaryophilic cell-permeable peptides into the nuclei of intact cells by covalently attached nuclear localization signals. Biochemistry 41:9208–9214

    Article  CAS  PubMed  Google Scholar 

  81. Mano M, Henriques A, Paiva A et al (2006) Cellular uptake of S413-PV peptide occurs upon conformational changes induced by peptide-membrane interactions. Biochim Biophys Acta 1758:336–346

    Article  CAS  PubMed  Google Scholar 

  82. Soomets U, Lindgren M, Gallet X et al (2000) Deletion analogues of transportan. Biochim Biophys Acta 1467:165–176

    Article  CAS  PubMed  Google Scholar 

  83. Johansson HJ, El-Andaloussi S, Holm T et al (2008) Characterization of a novel cytotoxic cell-penetrating peptide derived from p14ARF protein. Mol Ther 16:115–123

    Article  CAS  PubMed  Google Scholar 

  84. Lundberg P, Magzoub M, Lindberg M et al (2002) Cell membrane translocation of the N-terminal (1-28) part of the prion protein. Biochem Biophys Res Commun 299:85–90

    Article  CAS  PubMed  Google Scholar 

  85. Magzoub M, Sandgren S, Lundberg P et al (2006) N-terminal peptides from unprocessed prion proteins enter cells by macropinocytosis. Biochem Biophys Res Commun 348:379–385

    Article  CAS  PubMed  Google Scholar 

  86. El-Andaloussi S, Johansson HJ, Holm T et al (2007) A novel cell-penetrating peptide, M918, for efficient delivery of proteins and peptide nucleic acids. Mol Ther 15:1820–1826

    Article  CAS  PubMed  Google Scholar 

  87. Lorents A, Kodavali PK, Oskolkov N et al (2012) Cell-penetrating peptides split into two groups based on modulation of intracellular calcium concentration. J Biol Chem 287:16880–16889

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  88. Palm-Apergi C, Lorents A, Padari K et al (2009) The membrane repair response masks membrane disturbances caused by cell-penetrating peptide uptake. FASEB J 23:214–223

    Article  CAS  PubMed  Google Scholar 

  89. Oehlke J, Krause E, Wiesner B et al (1997) Extensive cellular uptake into endothelial cells of an amphipathic beta- sheet forming peptide. FEBS Lett 415:196–199

    Article  CAS  PubMed  Google Scholar 

  90. Magzoub M, Eriksson LE, Gräslund A (2002) Conformational states of the cell-penetrating peptide penetratin when interacting with phospholipid vesicles: effects of surface charge and peptide concentration. Biochim Biophys Acta 1563:53–63

    Article  CAS  PubMed  Google Scholar 

  91. Li W, Nicol F, Szoka FC Jr (2004) GALA: a designed synthetic pH-responsive amphipathic peptide with applications in drug and gene delivery. Adv Drug Deliv Rev 56:967–985

    Article  CAS  PubMed  Google Scholar 

  92. Sadler K, Eom KD, Yang JL et al (2002) Translocating proline-rich peptides from the antimicrobial peptide bactenecin 7. Biochemistry 41:14150–14157

    Article  CAS  PubMed  Google Scholar 

  93. Rojas M, Donahue JP, Tan Z et al (1998) Genetic engineering of proteins with cell membrane permeability. Nat Biotechnol 16:370–375

    Article  CAS  PubMed  Google Scholar 

  94. Gao C, Mao S, Ditzel HJ et al (2002) A cell-penetrating peptide from a novel pVII-pIX phage-displayed random peptide library. Bioorg Med Chem 10:4057–4065

    Article  CAS  PubMed  Google Scholar 

  95. Gao S, Simon MJ, Hue CD et al (2011) An unusual cell penetrating peptide identified using a plasmid display-based functional selection platform. ACS Chem Biol 6:484–491

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  96. Rhee M, Davis P (2006) Mechanism of uptake of C105Y, a novel cell-penetrating peptide. J Biol Chem 281:1233–1240

    Article  CAS  PubMed  Google Scholar 

  97. Jones S, Lukanowska M, Suhorutsenko J et al (2013) Intracellular translocation and differential accumulation of cell-penetrating peptides in bovine spermatozoa: evaluation of efficient delivery vectors that do not compromise human sperm motility. Hum Reprod 28:1874–1889

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  98. Sagan S, Burlina F, Alves ID et al (2013) Homeoproteins and homeoprotein-derived peptides: going in and out. Curr Pharm Des 19:2851–2862

    Article  CAS  PubMed  Google Scholar 

  99. Jones AT, Sayers EJ (2012) Cell entry of cell penetrating peptides: tales of tails wagging dogs. J Control Release 161:582–591

    Article  CAS  PubMed  Google Scholar 

  100. Räägel H, Säälik P, Pooga M (2010) Peptide-mediated protein delivery - which pathways are penetrable? Biochim Biophys Acta 1798:2240–2248

    Google Scholar 

  101. Duchardt F, Fotin-Mleczek M, Schwarz H et al (2007) A comprehensive model for the cellular uptake of cationic cell-penetrating peptides. Traffic 8:848–866

    Article  CAS  PubMed  Google Scholar 

  102. Fretz MM, Penning NA, Al-Taei S 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. Biochem J 403:335–342

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  103. Bechara C, Sagan S (2013) Cell-penetrating peptides: 20 years later, where do we stand? FEBS Lett 587:1693–1702

    Article  CAS  PubMed  Google Scholar 

  104. Richard JP, Melikov K, Vives E et al (2003) Cell-penetrating peptides. A reevaluation of the mechanism of cellular uptake. J Biol Chem 278:585–590

    Article  CAS  PubMed  Google Scholar 

  105. Fittipaldi A, Ferrari A, Zoppe M et al (2003) Cell membrane lipid rafts mediate caveolar endocytosis of HIV-1 Tat fusion proteins. J Biol Chem 278:34141–34149

    Article  CAS  PubMed  Google Scholar 

  106. Wadia JS, Stan RV, Dowdy SF (2004) Transducible TAT-HA fusogenic peptide enhances escape of TAT-fusion proteins after lipid raft macropinocytosis. Nat Med 10:310–315

    Article  CAS  PubMed  Google Scholar 

  107. Padari K, Säälik P, Hansen M et al (2005) Cell transduction pathways of transportans. Bioconjug Chem 16:1399–1410

    Article  CAS  PubMed  Google Scholar 

  108. Säälik P, Padari K, Niinep A et al (2009) Protein delivery with transportans is mediated by caveolae rather than flotillin-dependent pathways. Bioconjug Chem 20:877–887

    Article  PubMed  CAS  Google Scholar 

  109. Al Soraj M, He L, Peynshaert 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. J Control Release 161:132–141

    Article  CAS  PubMed  Google Scholar 

  110. Gerbal-Chaloin S, Gondeau C, Aldrian-Herrada G et al (2007) First step of the cell-penetrating peptide mechanism involves Rac1 GTPase-dependent actin-network remodelling. Biol Cell 99:223–238

    Article  CAS  PubMed  Google Scholar 

  111. Letoha T, Keller-Pinter A, Kusz E et al (2010) Cell-penetrating peptide exploited syndecans. Biochim Biophys Acta 1798:2258–2265

    Article  CAS  PubMed  Google Scholar 

  112. Tanaka G, Nakase I, Fukuda Y et al (2012) CXCR4 stimulates macropinocytosis: implications for cellular uptake of arginine-rich cell-penetrating peptides and HIV. Chem Biol 19:1437–1446

    Article  CAS  PubMed  Google Scholar 

  113. Gump JM, June RK, Dowdy SF (2010) Revised role of glycosaminoglycans in TAT protein transduction domain-mediated cellular transduction. J Biol Chem 285:1500–1507

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  114. Pae J, Säälik P, Liivamägi L et al (2014) Translocation of cell-penetrating peptides across the plasma membrane is controlled by cholesterol and microenvironment created by membranous proteins. J Control Release 192:103–113

    Article  CAS  PubMed  Google Scholar 

  115. Bryant KL, Mancias JD, Kimmelman AC et al (2014) KRAS: feeding pancreatic cancer proliferation. Trends Biochem Sci 39:91–100

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  116. Lehto T, Castillo Alvarez A, Gauck S et al (2014) Cellular trafficking determines the exon skipping activity of Pip6a-PMO in mdx skeletal and cardiac muscle cells. Nucleic Acids Res 42:3207–3217

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  117. Watkins CL, Schmaljohann D, Futaki S et al (2009) Low concentration thresholds of plasma membranes for rapid energy-independent translocation of a cell-penetrating peptide. Biochem J 420:179–189

    Article  CAS  PubMed  Google Scholar 

  118. Verdurmen WP, Thanos M, Ruttekolk IR et al (2010) Cationic cell-penetrating peptides induce ceramide formation via acid sphingomyelinase: implications for uptake. J Control Release 147:171–179

    Article  CAS  PubMed  Google Scholar 

  119. Herce HD, Garcia AE, Cardoso MC (2014) Fundamental molecular mechanism for the cellular uptake of guanidinium-rich molecules. J Am Chem Soc 136:17459

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Takeuchi T, Kosuge M, Tadokoro A et al (2006) Direct and rapid cytosolic delivery using cell-penetrating peptides mediated by pyrenebutyrate. ACS Chem Biol 1:299–303

    Article  CAS  PubMed  Google Scholar 

  121. Mishra A, Lai GH, Schmidt NW et al (2011) Translocation of HIV TAT peptide and analogues induced by multiplexed membrane and cytoskeletal interactions. Proc Natl Acad Sci U S A 108:16883–16888

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  122. Chen X, Sa’adedin F, Deme B et al (2013) Insertion of TAT peptide and perturbation of negatively charged model phospholipid bilayer revealed by neutron diffraction. Biochim Biophys Acta 1828:1982–1988

    Article  CAS  PubMed  Google Scholar 

  123. Deshayes S, Plenat T, Charnet P et al (2006) Formation of transmembrane ionic channels of primary amphipathic cell-penetrating peptides. Consequences on the mechanism of cell penetration. Biochim Biophys Acta 1758:1846–1851

    Article  CAS  PubMed  Google Scholar 

  124. Rydstrom A, Deshayes S, Konate K et al (2011) Direct translocation as major cellular uptake for CADY self-assembling peptide-based nanoparticles. PLoS One 6:e25924

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  125. Joliot A, Prochiantz A (2008) Homeoproteins as natural penetratin cargoes with signaling properties. Adv Drug Deliv Rev 60:608–613

    Article  CAS  PubMed  Google Scholar 

  126. Layalle S, Volovitch M, Mugat B et al (2011) Engrailed homeoprotein acts as a signaling molecule in the developing fly. Development 138:2315–2323

    Article  CAS  PubMed  Google Scholar 

  127. Prochiantz A, Fuchs J, Di Nardo AA (2014) Postnatal signalling with homeoprotein transcription factors. Philos Trans R Soc Lond B Biol Sci 369:pii: 20130518. doi:10.1098/rstb.2013.0518

    Article  CAS  Google Scholar 

  128. Palm C, Jayamanne M, Kjellander M et al (2007) Peptide degradation is a critical determinant for cell-penetrating peptide uptake. Biochim Biophys Acta 1768:1769–1776

    Article  CAS  PubMed  Google Scholar 

  129. Padari K, Koppel K, Lorents A et al (2010) S4(13)-PV cell-penetrating peptide forms nanoparticle-like structures to gain entry into cells. Bioconjug Chem 21:774–783

    Article  CAS  PubMed  Google Scholar 

  130. Oskolkov N, Arukuusk P, Copolovici DM et al (2011) NickFects, phosphorylated derivatives of transportan 10 for cellular delivery of oligonucleotides. Int J Pept Res Ther 17:147–157

    Article  CAS  Google Scholar 

  131. Regberg J, Eriksson JN, Langel Ü (2013) Cell-penetrating peptides: from cell cultures to in vivo applications. Front Biosci (Elite Ed) 5:509–516

    Google Scholar 

  132. Zorko M, Langel Ü (2005) Cell-penetrating peptides: mechanism and kinetics of cargo delivery. Adv Drug Deliv Rev 57:529–545

    Article  CAS  PubMed  Google Scholar 

  133. Polyakov V, Sharma V, Dahlheimer JL et al (2000) Novel Tat-peptide chelates for direct transduction of technetium-99m and rhenium into human cells for imaging and radiotherapy. Bioconjug Chem 11:762–771

    Article  CAS  PubMed  Google Scholar 

  134. Drin G, Cottin S, Blanc E et al (2003) Studies on the internalization mechanism of cationic cell-penetrating peptides. J Biol Chem 278:31192–31201

    Article  CAS  PubMed  Google Scholar 

  135. Tünnemann G, Ter-Avetisyan G, Martin RM et al (2008) Live-cell analysis of cell penetration ability and toxicity of oligo-arginines. J Pept Sci 14:469–476

    Article  PubMed  CAS  Google Scholar 

  136. Suzuki T, Futaki S, Niwa M et al (2002) Possible existence of common internalization mechanisms among arginine-rich peptides. J Biol Chem 277:2437–2443

    Article  CAS  PubMed  Google Scholar 

  137. Jones SW, Christison R, Bundell K et al (2005) Characterisation of cell-penetrating peptide-mediated peptide delivery. Br J Pharmacol 145:1093–1102

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  138. Järver P, Mäger I, Langel Ü (2010) In vivo biodistribution and efficacy of peptide mediated delivery. Trends Pharmacol Sci 31:528–535

    Article  PubMed  CAS  Google Scholar 

  139. Säälik P, Elmquist A, Hansen M et al (2004) Protein cargo delivery properties of cell-penetrating peptides. A comparative study. Bioconjug Chem 15:1246–1253

    Article  PubMed  CAS  Google Scholar 

  140. Lehto T, Abes R, Oskolkov N et al (2010) Delivery of nucleic acids with a stearylated (RxR)4 peptide using a non-covalent co-incubation strategy. J Control Release 141:42–51

    Article  CAS  PubMed  Google Scholar 

  141. Hällbrink M, Florén A, Elmquist A et al (2001) Cargo delivery kinetics of cell-penetrating peptides. Biochim Biophys Acta 1515:101–109

    Article  PubMed  Google Scholar 

  142. Mäger I, Eiriksdottir E, Langel K et al (2010) Assessing the uptake kinetics and internalization mechanisms of cell-penetrating peptides using a quenched fluorescence assay. Biochim Biophys Acta 1798:338–343

    Article  PubMed  CAS  Google Scholar 

  143. Mäger I, Langel K, Lehto T et al (2012) The role of endocytosis on the uptake kinetics of luciferin-conjugated cell-penetrating peptides. Biochim Biophys Acta 1818:502–511

    Article  PubMed  CAS  Google Scholar 

  144. Hirose H, Takeuchi T, Osakada H et al (2012) Transient focal membrane deformation induced by arginine-rich peptides leads to their direct penetration into cells. Mol Ther 20:984–993

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  145. Jiao CY, Delaroche D, Burlina F et al (2009) Translocation and endocytosis for cell-penetrating peptide internalization. J Biol Chem 284:33957–33965

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  146. Sasaki Y, Minamizawa M, Ambo A et al (2008) Cell-penetrating peptide-conjugated XIAP-inhibitory cyclic hexapeptides enter into Jurkat cells and inhibit cell proliferation. FEBS J 275:6011–6021

    Article  CAS  PubMed  Google Scholar 

  147. Lättig-Tünnemann G, Prinz M, Hoffmann D et al (2011) Backbone rigidity and static presentation of guanidinium groups increases cellular uptake of arginine-rich cell-penetrating peptides. Nat Commun 2:453

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  148. Oh D, Nasrolahi Shirazi A, Northup K et al (2014) Enhanced cellular uptake of short polyarginine peptides through fatty acylation and cyclization. Mol Pharm 11:2845–2854

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  149. Futaki S, Ohashi W, Suzuki T et al (2001) Stearylated arginine-rich peptides: a new class of transfection systems. Bioconjug Chem 12:1005–1011

    Article  CAS  PubMed  Google Scholar 

  150. Lehto T, Kurrikoff K, Langel Ü (2012) Cell-penetrating peptides for the delivery of nucleic acids. Expert Opin Drug Deliv 9:823–836

    Article  CAS  PubMed  Google Scholar 

  151. Arukuusk P, Pärnaste L, Oskolkov N et al (2013) New generation of efficient peptide-based vectors, NickFects, for the delivery of nucleic acids. Biochim Biophys Acta 1828:1365–1373

    Article  CAS  PubMed  Google Scholar 

  152. Mäe M, El Andaloussi S, Lundin P et al (2009) A stearylated CPP for delivery of splice correcting oligonucleotides using a non-covalent co-incubation strategy. J Control Release 134:221–227

    Article  PubMed  CAS  Google Scholar 

  153. Lehto T, Simonson OE, Mäger I et al (2011) A peptide-based vector for efficient gene transfer in vitro and in vivo. Mol Ther 19:1457–1467

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  154. Andaloussi SE, Lehto T, Mäger I et al (2011) Design of a peptide-based vector, PepFect6, for efficient delivery of siRNA in cell culture and systemically in vivo. Nucleic Acids Res 39:3972–3987

    Article  PubMed  CAS  Google Scholar 

  155. Ezzat K, Andaloussi SE, Zaghloul EM et al (2011) PepFect 14, a novel cell-penetrating peptide for oligonucleotide delivery in solution and as solid formulation. Nucleic Acids Res 39:5284–5298

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  156. Arukuusk P, Pärnaste L, Margus H et al (2013) Differential endosomal pathways for radically modified peptide vectors. Bioconjug Chem 24:1721–1732

    Article  CAS  PubMed  Google Scholar 

  157. Ezzat K, Helmfors H, Tudoran O et al (2012) Scavenger receptor-mediated uptake of cell-penetrating peptide nanocomplexes with oligonucleotides. FASEB J 26:1172–1180

    Article  CAS  PubMed  Google Scholar 

  158. Lindberg S, Munoz-Alarcon A, Helmfors H et al (2013) PepFect15, a novel endosomolytic cell-penetrating peptide for oligonucleotide delivery via scavenger receptors. Int J Pharm 441:242–247

    Article  CAS  PubMed  Google Scholar 

  159. Covic L, Gresser AL, Talavera J et al (2002) Activation and inhibition of G protein-coupled receptors by cell-penetrating membrane-tethered peptides. Proc Natl Acad Sci U S A 99:643–648

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  160. Tressel SL, Koukos G, Tchernychev B et al (2011) Pharmacology, biodistribution, and efficacy of GPCR-based pepducins in disease models. Methods Mol Biol 683:259–275

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  161. Leger AJ, Jacques SL, Badar J et al (2006) Blocking the protease-activated receptor 1-4 heterodimer in platelet-mediated thrombosis. Circulation 113:1244–1254

    Article  CAS  PubMed  Google Scholar 

  162. Boire A, Covic L, Agarwal A et al (2005) PAR1 is a matrix metalloprotease-1 receptor that promotes invasion and tumorigenesis of breast cancer cells. Cell 120:303–313

    Article  CAS  PubMed  Google Scholar 

  163. Kaneider NC, Agarwal A, Leger AJ et al (2005) Reversing systemic inflammatory response syndrome with chemokine receptor pepducins. Nat Med 11:661–665

    Article  CAS  PubMed  Google Scholar 

  164. Ochocki JD, Mullen DG, Wattenberg EV et al (2011) Evaluation of a cell penetrating prenylated peptide lacking an intrinsic fluorophore via in situ click reaction. Bioorg Med Chem Lett 21:4998–5001

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  165. Wollack JW, Zeliadt NA, Ochocki JD et al (2010) Investigation of the sequence and length dependence for cell-penetrating prenylated peptides. Bioorg Med Chem Lett 20:161–163

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  166. Bernal F, Tyler AF, Korsmeyer SJ et al (2007) Reactivation of the p53 tumor suppressor pathway by a stapled p53 peptide. J Am Chem Soc 129:2456–2457

    Article  CAS  PubMed  Google Scholar 

  167. Walensky LD, Kung AL, Escher I et al (2004) Activation of apoptosis in vivo by a hydrocarbon-stapled BH3 helix. Science 305:1466–1470

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  168. Brown CJ, Quah ST, Jong J et al (2013) Stapled peptides with improved potency and specificity that activate p53. ACS Chem Biol 8:506–512

    Article  CAS  PubMed  Google Scholar 

  169. Betts C, Saleh AF, Arzumanov AA et al (2012) Pip6-PMO, a new generation of peptide-oligonucleotide conjugates with improved cardiac exon skipping activity for dmd treatment. Mol Ther Nucleic Acids 1:e38

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  170. Järver P, Coursindel T, Andaloussi SE et al (2012) Peptide-mediated cell and in vivo delivery of antisense oligonucleotides and siRNA. Mol Ther Nucleic Acids 1:e27

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  171. Sugahara KN, Teesalu T, Karmali PP et al (2009) Tissue-penetrating delivery of compounds and nanoparticles into tumors. Cancer Cell 16:510–520

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  172. Teesalu T, Sugahara KN, Kotamraju VR et al (2009) C-end rule peptides mediate neuropilin-1-dependent cell, vascular, and tissue penetration. Proc Natl Acad Sci U S A 106:16157–16162

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  173. Alvarez-Erviti L, Seow Y, Yin H et al (2011) Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol 29:341–345

    Article  CAS  PubMed  Google Scholar 

  174. El-Andaloussi S, Lee Y, Lakhal-Littleton S et al (2012) Exosome-mediated delivery of siRNA in vitro and in vivo. Nat Protoc 7:2112–2126

    Article  CAS  PubMed  Google Scholar 

  175. Lang BT, Cregg JM, DePaul MA et al (2015) Modulation of the proteoglycan receptor PTPsigma promotes recovery after spinal cord injury. Nature 518:404–408

    Google Scholar 

  176. Kobayashi S, Takeshima K, Park CB et al (2000) Interactions of the novel antimicrobial peptide buforin 2 with lipid bilayers: proline as a translocation promoting factor. Biochemistry 39:8648–8654

    Article  CAS  PubMed  Google Scholar 

  177. Kerkis A, Kerkis I, Radis-Baptista G et al (2004) Crotamine is a novel cell-penetrating protein from the venom of rattlesnake Crotalus durissus terrificus. FASEB J 18:1407–1409

    CAS  PubMed  Google Scholar 

  178. Taylor BN, Mehta RR, Yamada T et al (2009) Noncationic peptides obtained from azurin preferentially enter cancer cells. Cancer Res 69:537–546

    Article  CAS  PubMed  Google Scholar 

  179. Trehin R, Krauss U, Beck-Sickinger AG et al (2004) Cellular uptake but low permeation of human calcitonin-derived cell penetrating peptides and Tat(47-57) through well-differentiated epithelial models. Pharm Res 21:1248–1256

    Article  CAS  PubMed  Google Scholar 

  180. Delaroche D, Aussedat B, Aubry S et al (2007) Tracking a new cell-penetrating (W/R) nonapeptide, through an enzyme-stable mass spectrometry reporter tag. Anal Chem 79:1932–1938

    Article  CAS  PubMed  Google Scholar 

  181. Oehlke J, Scheller A, Wiesner B et al (1998) Cellular uptake of an alpha-helical amphipathic model peptide with the potential to deliver polar compounds into the cell interior non- endocytically. Biochim Biophys Acta 1414:127–139

    Article  CAS  PubMed  Google Scholar 

  182. Scheller A, Oehlke J, Wiesner B et al (1999) Structural requirements for cellular uptake of alpha-helical amphipathic peptides. J Pept Sci 5:185–194

    Article  CAS  PubMed  Google Scholar 

  183. Daniels DS, Schepartz A (2007) Intrinsically cell-permeable miniature proteins based on a minimal cationic PPII motif. J Am Chem Soc 129:14578–14579

    Article  CAS  PubMed  Google Scholar 

  184. Martin I, Teixido M, Giralt E (2011) Design, synthesis and characterization of a new anionic cell-penetrating peptide: SAP(E). Chembiochem 12:896–903

    Article  CAS  PubMed  Google Scholar 

  185. Lindgren M, Rosenthal-Aizman K, Saar K et al (2006) Overcoming methotrexate resistance in breast cancer tumour cells by the use of a new cell-penetrating peptide. Biochem Pharmacol 71:416–425

    Article  CAS  PubMed  Google Scholar 

  186. Covic L, Misra M, Badar J et al (2002) Pepducin-based intervention of thrombin-receptor signaling and systemic platelet activation. Nat Med 8:1161–1165

    Article  CAS  PubMed  Google Scholar 

  187. Forsman H, Bylund J, Oprea TI et al (2013) The leukocyte chemotactic receptor FPR2, but not the closely related FPR1, is sensitive to cell-penetrating pepducins with amino acid sequences descending from the third intracellular receptor loop. Biochim Biophys Acta 1833:1914–1923

    Article  CAS  PubMed  Google Scholar 

  188. Lin YZ, Yao SY, Veach RA et al (1995) Inhibition of nuclear translocation of transcription factor NF-kappa B by a synthetic peptide containing a cell membrane-permeable motif and nuclear localization sequence. J Biol Chem 270:14255–14258

    Article  CAS  PubMed  Google Scholar 

  189. Gomez JA, Gama V, Yoshida T et al (2007) Bax-inhibiting peptides derived from Ku70 and cell-penetrating pentapeptides. Biochem Soc Trans 35:797–801

    Article  CAS  PubMed  Google Scholar 

  190. Gomez JA, Chen J, Ngo J et al (2010) Cell-penetrating penta-peptides (CPP5s): measurement of cell entry and protein-transduction activity. Pharmaceuticals (Basel) 3:3594–3613

    Article  CAS  Google Scholar 

  191. Marks JR, Placone J, Hristova K et al (2011) Spontaneous membrane-translocating peptides by orthogonal high-throughput screening. J Am Chem Soc 133:8995–9004

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  192. Oehlke J, Birth P, Klauschenz E et al (2002) Cellular uptake of antisense oligonucleotides after complexing or conjugation with cell-penetrating model peptides. Eur J Biochem 269:4025–4032

    Article  CAS  PubMed  Google Scholar 

  193. Chee SM, Wongsantichon J, Soo Tng Q et al (2014) Structure of a stapled peptide antagonist bound to nutlin-resistant Mdm2. PLoS One 9:e104914

    Article  PubMed Central  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We are grateful to Dr. A. Lorents for the help with table and citations. The authors were supported by grants from the Estonian Science Foundation (ESF 8705), the Estonian Ministry of Education and Research (0180019s11, 0180027s08), and European Union Regional Development Fund (grant EU30020) through the Competence Centre on Reproductive Medicine and Biology.

Author information

Authors and Affiliations

  1. Institute of Molecular and Cell Biology, University of Tartu, 23a Riia Street, Tartu, 51010, Estonia

    Margus Pooga

  2. Department of Neurochemistry, Stockholm University, Stockholm, Sweden

    Ülo Langel

  3. Laboratory of Molecular Biotechnology, Institute of Technology, Tartu University, Tartu, Estonia

    Ülo Langel

Authors
  1. Margus Pooga
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ülo Langel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Margus Pooga .

Editor information

Editors and Affiliations

  1. Department of Neurochemistry, Stockholm University, Stockholm, Sweden

    Ülo Langel

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Science+Business Media New York

About this protocol

Cite this protocol

Pooga, M., Langel, Ü. (2015). Classes of Cell-Penetrating Peptides. In: Langel, Ü. (eds) Cell-Penetrating Peptides. Methods in Molecular Biology, vol 1324. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2806-4_1

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-2806-4_1

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-2805-7

  • Online ISBN: 978-1-4939-2806-4

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation