1932

Abstract

Protein-protein interactions are fundamental for virtually all functions of the cell. A large fraction of these interactions involve short peptide motifs, and there has been increased interest in targeting them using peptide-based therapeutics. Peptides benefit from being specific, relatively safe, and easy to produce. They are also easy to modify using chemical synthesis and molecular biology techniques. However, significant challenges remain regarding the use of peptides as therapeutic agents. Identification of peptide motifs is difficult, and peptides typically display low cell permeability and sensitivity to enzymatic degradation. In this review, we outline the principal high-throughput methodologies for motif discovery and describe current methods for overcoming pharmacokinetic and bioavailability limitations.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-pharmtox-010716-104805
2017-01-06
2024-10-07
Loading full text...

Full text loading...

/deliver/fulltext/pharmtox/57/1/annurev-pharmtox-010716-104805.html?itemId=/content/journals/10.1146/annurev-pharmtox-010716-104805&mimeType=html&fmt=ahah

Literature Cited

  1. Stumpf MPH, Thorne T, de Silva E, Stewart R, An HJ. 1.  et al. 2008. Estimating the size of the human interactome. PNAS 105:196959–64 [Google Scholar]
  2. Neduva V, Russell RB. 2.  2006. Peptides mediating interaction networks: new leads at last. Curr. Opin. Biotechnol. 17:5465–71 [Google Scholar]
  3. Fosgerau K, Hoffmann T. 3.  2015. Peptide therapeutics: current status and future directions. Drug Discov. Today 20:1122–28 [Google Scholar]
  4. Vanhee P, Reumers J, Stricher F, Baeten L, Serrano L. 4.  et al. 2010. PepX: a structural database of non-redundant protein-peptide complexes. Nucl. Acids Res. 38:Suppl. 1D545–51 [Google Scholar]
  5. Perkins JR, Diboun I, Dessailly BH, Lees JG, Orengo C. 5.  2010. Transient protein-protein interactions: structural, functional, and network properties. Structure 18:101233–43 [Google Scholar]
  6. Koivunen E, Wang B, Ruoslahti E. 6.  1995. Phage libraries displaying cyclic peptides with different ring sizes: ligand specificities of the RGD-directed integrins. Biotechnology 13:3265–70 [Google Scholar]
  7. Molek P, Strukelj B, Bratkovic T. 7.  2011. Peptide phage display as a tool for drug discovery: targeting membrane receptors. Molecules 16:1857–87 [Google Scholar]
  8. Corbi-Verge C, Kim PM. 8.  2016. Motif mediated protein-protein interactions as drug targets. Cell Commun. Signal. 14:18 [Google Scholar]
  9. Hamman JH, Enslin GM, Kotze AF. 9.  2005. Oral delivery of peptide drugs: barriers and developments. BioDrugs 19:3165–77 [Google Scholar]
  10. Murray JK, Gellman SH. 10.  2007. Targeting protein-protein interactions: lessons from p53/MDM2. Biopolymers 88:5657–86 [Google Scholar]
  11. Verdine GL, Walensky LD. 11.  2007. The challenge of drugging undruggable targets in cancer: lessons learned from targeting BCL-2 family members. Clin. Cancer Res. 13:247264–70 [Google Scholar]
  12. Hamzeh-Mivehroud M, Alizadeh AA, Morris MB, Church WB, Dastmalchi S. 12.  2013. Phage display as a technology delivering on the promise of peptide drug discovery. Drug Discov. Today 18:23–241144–57 [Google Scholar]
  13. Sergeeva A, Kolonin MG, Molldrem JJ, Pasqualini R, Arap W. 13.  2006. Display technologies: application for the discovery of drug and gene delivery agents. Adv. Drug Deliv. Rev. 58:151622–54 [Google Scholar]
  14. Sparks AB, Quilliam LA, Thorn JM, Der CJ, Kay BK. 14.  1994. Identification and characterization of Src SH3 ligands from phage-displayed random peptide libraries. J. Biol. Chem. 269:3923853–56 [Google Scholar]
  15. Fuh G, Pisabarro MT, Li Y, Quan C, Lasky LA, Sidhu SS. 15.  2000. Analysis of PDZ domain-ligand interactions using carboxyl-terminal phage display. J. Biol. Chem. 275:2821486–91 [Google Scholar]
  16. Ivarsson Y, Arnold R, McLaughlin M, Nim S, Joshi R. 16.  et al. 2014. Large-scale interaction profiling of PDZ domains through proteomic peptide-phage display using human and viral phage peptidomes. PNAS 111:72542–47 [Google Scholar]
  17. Locatelli F, Del Vecchio L. 17.  2009. Hematide™ for the treatment of chronic kidney disease-related anemia. Expert Rev. Hematol. 2:4377–83 [Google Scholar]
  18. Giordano RJ, Cardó-Vila M, Salameh A, Anobom CD, Zeitlin BD. 18.  et al. 2010. From combinatorial peptide selection to drug prototype (I): targeting the vascular endothelial growth factor receptor pathway. PNAS 107:115112–17 [Google Scholar]
  19. Koivunen E, Gay DA, Ruoslahti E. 19.  1993. Selection of peptides binding to the α5β1 integrin from phage display library. J. Biol. Chem. 268:2720205–10 [Google Scholar]
  20. Sundell GN, Ivarsson Y. 20.  2014. Interaction analysis through proteomic phage display. BioMed. Res. Int. 2014:176172 [Google Scholar]
  21. Luck K, Travé G. 21.  2011. Phage display can select over-hydrophobic sequences that may impair prediction of natural domain–peptide interactions. Bioinformatics 27:7899–902 [Google Scholar]
  22. Blikstad C, Ivarsson Y. 22.  2015. High-throughput methods for identification of protein-protein interactions involving short linear motifs. Cell Commun. Signal. 13:16959 [Google Scholar]
  23. Plückthun A. 23.  2012. Ribosome display: a perspective. Methods in Molecular Biology, Vol. 805 Ribosome Display and Related Technologies3–28 New York: Springer [Google Scholar]
  24. Wang H, Liu R. 24.  2011. Advantages of mRNA display selections over other selection techniques for investigation of protein-protein interactions. Expert Rev. Proteom. 8:3335–46 [Google Scholar]
  25. Wada A. 25.  2013. Development of next-generation peptide binders using in vitro display technologies and their potential applications. Front. Immunol. 4:224 [Google Scholar]
  26. Cotten SW, Zou J, Wang R, Huang B-C, Liu R. 26.  2011. mRNA display-based selections using synthetic peptide and natural protein libraries. Methods in Molecular Biology, Vol. 805 Ribosome Display and Related Technologies287–97 New York: Springer [Google Scholar]
  27. Wu H, Hu Z, Liu XQ. 27.  1998. Protein trans-splicing by a split intein encoded in a split DnaE gene of Synechocystis sp. PCC6803. PNAS 95:169226–31 [Google Scholar]
  28. Tavassoli A, Benkovic SJ. 28.  2007. Split-intein mediated circular ligation used in the synthesis of cyclic peptide libraries in E. coli. Nat. Protoc. 2:51126–33 [Google Scholar]
  29. Horswill AR, Savinov SN, Benkovic SJ. 29.  2004. A systematic method for identifying small-molecule modulators of protein-protein interactions. PNAS 101:4415591–96 [Google Scholar]
  30. Lennard KR, Tavassoli A. 30.  2014. Peptides come round: using SICLOPPS libraries for early stage drug discovery. Chem. Eur. J. 20:3410608–14 [Google Scholar]
  31. Nim S, Jeon J, Corbi-Verge C, Seo M-H, Ivarsson Y. 31.  et al. 2016. Pooled screening for antiproliferative inhibitors of protein-protein interactions. Nat. Chem. Biol. 12:275–81 [Google Scholar]
  32. Sims D, Mendes-Pereira AM, Frankum J, Burgess D, Cerone M-A. 32.  et al. 2011. High-throughput RNA interference screening using pooled shRNA libraries and next generation sequencing. Genome Biol 12:10R104 [Google Scholar]
  33. Fodor S, Read J, Pirrung M, Stryer L, Lu A, Solas D. 33.  1991. Light-directed, spatially addressable parallel chemical synthesis. Science 251:4995767–73 [Google Scholar]
  34. Frank R. 34.  1992. Spot-synthesis: an easy technique for the positionally addressable, parallel chemical synthesis on a membrane support. Tetrahedron 48:429217–32 [Google Scholar]
  35. Pellois JP, Zhou X, Srivannavit O, Zhou T, Gulari E, Gao X. 35.  2002. Individually addressable parallel peptide synthesis on microchips. Nat. Biotechnol. 20:9922–26 [Google Scholar]
  36. Li S, Marthandan N, Bowerman D, Garner HR, Kodadek T. 36.  2005. Photolithographic synthesis of cyclic peptide arrays using a differential deprotection strategy. Chem. Commun. 2005:581–83 [Google Scholar]
  37. Winkler DFH, Andresen H, Hilpert K. 37.  2011. SPOT synthesis as a tool to study protein-protein interactions. Methods in Molecular Biology, Vol. 723 Protein Microarray for Disease Analysis105–27 New York: Springer [Google Scholar]
  38. Tinti M, Kiemer L, Costa S, Miller ML, Sacco F. 38.  et al. 2013. The SH2 domain interaction landscape. Cell Rep 3:41293–305 [Google Scholar]
  39. Carmona SJ, Nielsen M, Schafer-Nielsen C, Mucci J, Altcheh J. 39.  et al. 2015. Towards high-throughput immunomics for infectious diseases: use of next-generation peptide microarrays for rapid discovery and mapping of antigenic determinants. Mol. Cell Proteom. 14:71871–84 [Google Scholar]
  40. Cretich M, Longhi R, Corti A, Damin F, Di Carlo G. 40.  et al. 2009. Epitope mapping of human chromogranin A by peptide microarrays. Methods in Molecular Biology, Vol. 570 Peptide Microarrays221–32 New York: Springer. [Google Scholar]
  41. Okada H, Uezu A, Soderblom EJ, Moseley MA, Gertler FB, Soderling SH. 41.  2012. Peptide array X-linking (PAX): a new peptide-protein identification approach. PLOS ONE 7:5e37035 [Google Scholar]
  42. Diehnelt CW. 42.  2013. Peptide array based discovery of synthetic antimicrobial peptides. Front. Microbiol. 4:402 [Google Scholar]
  43. Rayburn E, Zhang R, He J, Wang H. 43.  2005. MDM2 and human malignancies: expression, clinical pathology, prognostic markers, and implications for chemotherapy. Curr. Cancer Drug Targets 5:127–41 [Google Scholar]
  44. Cesa LC, Patury S, Komiyama T, Ahmad A, Zuiderweg ERP, Gestwicki JE. 44.  2013. Inhibitors of difficult protein-protein interactions identified by high-throughput screening of multiprotein complexes. ACS Chem. Biol. 8:91988–97 [Google Scholar]
  45. Ballard CE, Yu H, Wang B. 45.  2002. Recent developments in depsipeptide research. Curr. Med. Chem 94471–98 [Google Scholar]
  46. Sarabia F, Chammaa S, Ruiz AS, Ortiz LM, Herrera FJL. 46.  2004. Chemistry and biology of cyclic depsipeptides of medicinal and biological interest. Curr. Med. Chem 11101309–32 [Google Scholar]
  47. VanderMolen KM, McCulloch W, Pearce CJ, Oberlies NH. 47.  2011. Romidepsin (Istodax, NSC 630176, FR901228, FK228, depsipeptide): a natural product recently approved for cutaneous T-cell lymphoma. J. Antibiot. 64:8525–31 [Google Scholar]
  48. Haste NM, Thienphrapa W, Tran DN, Loesgen S, Sun P. 48.  et al. 2012. Activity of the thiopeptide antibiotic nosiheptide against contemporary strains of methicillin-resistant Staphylococcus aureus. J. Antibiot. 65:12593–98 [Google Scholar]
  49. Romero F, Espliego F, Pérez Baz J, García de Quesada T, Grávalos D. 49.  et al. 1997. Thiocoraline, a new depsipeptide with antitumor activity produced by a marine Micromonospora. I. Taxonomy, fermentation, isolation, and biological activities. J. Antibiot. 50:9734–37 [Google Scholar]
  50. Kang YK, Byun BJ. 50.  2008. Conformational preferences and cis–trans isomerization of l-lactic acid residue. J. Phys. Chem. B 112:309126–34 [Google Scholar]
  51. Liebman JF, Greenberg A. 51.  1974. The origin of rotational barriers in amides and esters. Biophys. Chem. 1:3222–26 [Google Scholar]
  52. Qu H, Magotti P, Ricklin D, Wu EL, Kourtzelis I. 52.  et al. 2011. Novel analogues of the therapeutic complement inhibitor compstatin with significantly improved affinity and potency. Mol. Immunol. 48:4481–89 [Google Scholar]
  53. Magrath J, Abeles RH. 53.  1992. Cysteine protease inhibition by azapeptide esters. J. Med. Chem 35234279–83 [Google Scholar]
  54. Xing R, Hanzlik RP. 54.  1998. Azapeptides as inhibitors and active site titrants for cysteine proteinases. J. Med. Chem 4181344–51 [Google Scholar]
  55. von Hentig N. 55.  2008. Atazanavir/ritonavir: a review of its use in HIV therapy. Drugs Today 44:2103–32 [Google Scholar]
  56. Han H, Yoon J, Janda KD. 56.  1999. Azatides as peptidomimetics: solution and liquid phase syntheses. Methods in Molecular Medicine, Vol. 23 Peptidomimetics Protocols87–102 Totowa, NJ: Humana Press [Google Scholar]
  57. Dyker H, Scherkenbeck J, Gondol D, Goehrt A, Harder A. 57.  2001. Azadepsipeptides: synthesis and evaluation of a novel class of peptidomimetics. J. Org. Chem. 66:113760–66 [Google Scholar]
  58. Cheng RP, Gellman SH, DeGrado WF. 58.  2001. β-Peptides: from structure to function. Chem. Rev. 101:103219–32 [Google Scholar]
  59. Murray JK, Farooqi B, Sadowsky JD, Scalf M, Freund WA. 59.  et al. 2005. Efficient synthesis of a β-peptide combinatorial library with microwave irradiation. J. Am. Chem. Soc. 127:3813271–80 [Google Scholar]
  60. Frackenpohl J, Arvidsson PI, Schreiber JV, Seebach D. 60.  2001. The outstanding biological stability of β- and γ-peptides toward proteolytic enzymes: an in vitro investigation with fifteen peptidases. ChemBioChem 2:6445–55 [Google Scholar]
  61. Vickers CJ, González-Páez GE, Litwin KM, Umotoy JC, Coutsias EA, Wolan DW. 61.  2014. Selective inhibition of initiator versus executioner caspases using small peptides containing unnatural amino acids. ACS Chem. Biol. 9:102194–98 [Google Scholar]
  62. Gfeller D, Michielin O, Zoete V. 62.  2013. SwissSidechain: a molecular and structural database of non-natural sidechains. Nucl. Acids Res. 41:D1D327–32 [Google Scholar]
  63. Young TS, Schultz PG. 63.  2010. Beyond the canonical 20 amino acids: expanding the genetic lexicon. J. Biol. Chem. 285:1511039–44 [Google Scholar]
  64. Wu C-H, Chen Y-P, Mou C-Y, Cheng RP. 64.  2013. Altering the Tat-derived peptide bioactivity landscape by changing the arginine side chain length. Amino Acids 44:2473–80 [Google Scholar]
  65. Omidfar K, Daneshpour M. 65.  2015. Advances in phage display technology for drug discovery. Expert Opin. Drug Discov. 10:6651–69 [Google Scholar]
  66. Renfrew PD, Choi EJ, Bonneau R, Kuhlman B. 66.  2012. Incorporation of noncanonical amino acids into Rosetta and use in computational protein-peptide interface design. PLOS ONE 7:3e32637 [Google Scholar]
  67. Khoury GA, Smadbeck J, Tamamis P, Vandris AC, Kieslich CA, Floudas CA. 67.  2014. Forcefield_NCAA: ab initio charge parameters to aid in the discovery and design of therapeutic proteins and peptides with unnatural amino acids and their application to complement inhibitors of the compstatin family. ACS Synth. Biol. 3:12855–69 [Google Scholar]
  68. Reddy MR, Reddy CR, Rathore RS, Erion MD, Aparoy P. 68.  et al. 2014. Free energy calculations to estimate ligand-binding affinities in structure-based drug design. Curr. Pharm. Des. 20:203323–37 [Google Scholar]
  69. Nickl CK, Raidas SK, Zhao H, Sausbier M, Ruth P. 69.  et al. 2010. (d)-Amino acid analogues of DT-2 as highly selective and superior inhibitors of cGMP-dependent protein kinase Iα.. Biochim. Biophys. Acta 1804:3524–32 [Google Scholar]
  70. Brugidou J, Legrand C, Mery J, Rabie A. 70.  1995. The retro-inverso form of a homeobox-derived short peptide is rapidly internalised by cultured neurones: a new basis for an efficient intracellular delivery system. Biochem. Biophys. Res. Commun. 214:2685–93 [Google Scholar]
  71. Rabideau AE, Pentelute BL. 71.  2015. A d-amino acid at the N-terminus of a protein abrogates its degradation by the N-end rule pathway. ACS Cent. Sci. 1:8423–30 [Google Scholar]
  72. Veine DM, Yao H, Stafford DR, Fay KS, Livant DL. 72.  2014. A d-amino acid containing peptide as a potent, noncovalent inhibitor of α5β1 integrin in human prostate cancer invasion and lung colonization. Clin. Exp. Metastasis 31:4379–93 [Google Scholar]
  73. Bruno BJ, Miller GD, Lim CS. 73.  2013. Basics and recent advances in peptide and protein drug delivery. Ther. Deliv. 4:111443–67 [Google Scholar]
  74. Li C, Zhan C, Zhao L, Chen X, Lu W-Y, Lu W. 74.  2013. Functional consequences of retro-inverso isomerization of a miniature protein inhibitor of the p53-MDM2 interaction. Bioorg. Med. Chem 21144045–50 [Google Scholar]
  75. Parthsarathy V, McClean PL, Hölscher C, Taylor M, Tinker C. 75.  et al. 2013. A novel retro-inverso peptide inhibitor reduces amyloid deposition, oxidation and inflammation and stimulates neurogenesis in the APPswe/PS1ΔE9 mouse model of Alzheimer's disease. PLOS ONE 8:1e54769 [Google Scholar]
  76. Xie Z, Shen Q, Xie C, Lu W, Peng C. 76.  et al. 2015. Retro-inverso bradykinin opens the door of blood-brain tumor barrier for nanocarriers in glioma treatment. Cancer Lett 369:1144–51 [Google Scholar]
  77. Li C, Pazgier M, Li J, Li C, Liu M. 77.  et al. 2010. Limitations of peptide retro-inverso isomerization in molecular mimicry. J. Biol. Chem. 285:2519572–81 [Google Scholar]
  78. Schumacher TNM, Mayr LM, Minor DL Jr., Milhollen MA, Burgess MW, Kim PS. 78.  1996. Identification of d-peptide ligands through mirror-image phage display. Science 271:52571854–57 [Google Scholar]
  79. Weinstock MT, Jacobsen MT, Kay MS. 79.  2014. Synthesis and folding of a mirror-image enzyme reveals ambidextrous chaperone activity. PNAS 111:3211679–84 [Google Scholar]
  80. Rüdiger S, Schneider-Mergener J, Bukau B. 80.  2001. Its substrate specificity characterizes the DnaJ co-chaperone as a scanning factor for the DnaK chaperone. EMBO J 20:51042–50 [Google Scholar]
  81. Pfaff M, Tangemann K, Müller B, Gurrath M, Müller G. 81.  et al. 1994. Selective recognition of cyclic RGD peptides of NMR defined conformation by αIIbβ3, αVβ3, and α5β1 integrins. J. Biol. Chem. 269:3220233–38 [Google Scholar]
  82. Kessler H, Gratias R, Hessler G, Gurrath M, Müller G. 82.  1996. Conformation of cyclic peptides. Principle concepts and the design of selectivity and superactivity in bioactive sequences by “spatial screening.”. Pure Appl. Chem. 68:6 1201:5 [Google Scholar]
  83. Nabors LB, Mikkelsen T, Hegi ME, Ye X, Batchelor T. 83.  et al. 2012. A safety run-in and randomized phase 2 study of cilengitide combined with chemoradiation for newly diagnosed glioblastoma (NABTT 0306). Cancer 118:225601–7 [Google Scholar]
  84. Park BW, Zhang HT, Wu C, Berezov A, Zhang X. 84.  et al. 2000. Rationally designed anti-HER2/neu peptide mimetic disables P185HER2/neu tyrosine kinases in vitro and in vivo. Nat. Biotechnol. 18:2194–98 [Google Scholar]
  85. Rezai T, Yu B, Millhauser GL, Jacobson MP, Lokey RS. 85.  2006. Testing the conformational hypothesis of passive membrane permeability using synthetic cyclic peptide diastereomers. J. Am. Chem. Soc. 128:82510–11 [Google Scholar]
  86. Zinzalla G, Thurston DE. 86.  2009. Targeting protein-protein interactions for therapeutic intervention: a challenge for the future. Future Med. Chem 1165–93 [Google Scholar]
  87. Horton DA, Bourne GT, Smythe ML. 87.  2002. Exploring privileged structures: the combinatorial synthesis of cyclic peptides. Mol. Divers. 5:4289–304 [Google Scholar]
  88. Verdine GL, Hilinski GJ. 88.  2012. Stapled peptides for intracellular drug targets. Meth. Enzymol. 503:3–33 [Google Scholar]
  89. Schafmeister CE, Stroud RM. 89.  1998. Helical protein design. Curr. Opin. Biotechnol. 9:4350–53 [Google Scholar]
  90. Okamoto T, Zobel K, Fedorova A, Quan C, Yang H. 90.  et al. 2013. Stabilizing the pro-apoptotic BimBH3 helix (BimSAHB) does not necessarily enhance affinity or biological activity. ACS Chem. Biol. 8:2297–302 [Google Scholar]
  91. Bird GH, Gavathiotis E, LaBelle JL, Katz SG, Walensky LD. 91.  2014. Distinct BimBH3 (BimSAHB) stapled peptides for structural and cellular studies. ACS Chem. Biol. 9:3831–37 [Google Scholar]
  92. Walensky LD, Kung AL, Escher I, Malia TJ, Barbuto S. 92.  et al. 2004. Activation of apoptosis in vivo by a hydrocarbon-stapled BH3 helix. Science 305:56891466–70 [Google Scholar]
  93. Moellering RE, Cornejo M, Davis TN, Del Bianco C, Aster JC. 93.  et al. 2009. Direct inhibition of the NOTCH transcription factor complex. Nature 462:7270182–88 [Google Scholar]
  94. Bernal F, Tyler AF, Korsmeyer SJ, Walensky LD, Verdine GL. 94.  2007. Reactivation of the p53 tumor suppressor pathway by a stapled p53 peptide. J. Am. Chem. Soc. 129:92456–57 [Google Scholar]
  95. Chang YS, Graves B, Guerlavais V, Tovar C, Packman K. 95.  et al. 2013. Stapled α-helical peptide drug development: a potent dual inhibitor of MDM2 and MDMX for p53-dependent cancer therapy. PNAS 110:36E3445–54 [Google Scholar]
  96. Pechar M, Ulbrich K, Subr V, Seymour LW, Schacht EH. 96.  2000. Poly(ethylene glycol) multiblock copolymer as a carrier of anti-cancer drug doxorubicin. Bioconjug. Chem. 11:2131–39 [Google Scholar]
  97. Patel A, Cholkar K, Mitra AK. 97.  2014. Recent developments in protein and peptide parenteral delivery approaches. Ther. Deliv. 5:3337–65 [Google Scholar]
  98. Kumar TR, Soppimath K, Nachaegari SK. 98.  2006. Novel delivery technologies for protein and peptide therapeutics. Curr. Pharm. Biotechnol. 7:4261–76 [Google Scholar]
  99. Tan ML, Choong PF, Dass CR. 99.  2010. Recent developments in liposomes, microparticles and nanoparticles for protein and peptide drug delivery. Peptides 31:1184–93 [Google Scholar]
  100. Kintzer AF, Thoren KL, Sterling HJ, Dong KC, Feld GK. 100.  et al. 2009. The protective antigen component of anthrax toxin forms functional octameric complexes. J. Mol. Biol. 392:3614–29 [Google Scholar]
  101. Klumpp C, Kostarelos K, Prato M, Bianco A. 101.  2006. Functionalized carbon nanotubes as emerging nanovectors for the delivery of therapeutics. Biochim. Biophys. Acta 1758:3404–12 [Google Scholar]
  102. da Silva Freitas D, Mero A, Pasut G. 102.  2013. Chemical and enzymatic site specific PEGylation of hGH. Bioconjug. Chem. 24:3456–63 [Google Scholar]
  103. Xue X, Li D, Yu J, Ma G, Su Z, Hu T. 103.  2013. Phenyl linker-induced dense PEG conformation improves the efficacy of C-terminally monoPEGylated staphylokinase. Biomacromolecules 14:2331–41 [Google Scholar]
  104. Wang J, Wu D, Shen WC. 104.  2002. Structure-activity relationship of reversibly lipidized peptides: studies of fatty acid-desmopressin conjugates. Pharm. Res. 19:5609–14 [Google Scholar]
  105. Cheng W, Satyanarayanajois S, Lim LY. 105.  2007. Aqueous-soluble, non-reversible lipid conjugate of salmon calcitonin: synthesis, characterization and in vivo activity. Pharm. Res. 24:199–110 [Google Scholar]
  106. Havelund S, Plum A, Ribel U, Jonassen I, Volund A. 106.  et al. 2004. The mechanism of protraction of insulin detemir, a long-acting, acylated analog of human insulin. Pharm. Res. 21:81498–1504 [Google Scholar]
  107. Gault VA, Kerr BD, Harriott P, Flatt PR. 107.  2011. Administration of an acylated GLP-1 and GIP preparation provides added beneficial glucose-lowering and insulinotropic actions over single incretins in mice with Type 2 diabetes and obesity. Clin. Sci. 121:3107–17 [Google Scholar]
  108. Maletínská L, Nagelová V, Tichá A, Zemenová J, Pirník Z. 108.  et al. 2015. Novel lipidized analogs of prolactin-releasing peptide have prolonged half-lives and exert anti-obesity effects after peripheral administration. Int. J. Obes. 39:6986–93 [Google Scholar]
  109. Johannessen L, Remsberg J, Gaponenko V, Adams KM, Barchi JJ Jr.. 109.  et al. 2011. Peptide structure stabilization by membrane anchoring and its general applicability to the development of potent cell-permeable inhibitors. ChemBioChem 12:6914–21 [Google Scholar]
  110. Kocevar N, Obermajer N, Strukelj B, Kos J, Kreft S. 110.  2007. Improved acylation method enables efficient delivery of functional palmitoylated cystatin into epithelial cells. Chem. Biol. Drug Des. 69:2124–31 [Google Scholar]
  111. Pooga M, Langel Ü. 111.  2005. Synthesis of cell-penetrating peptides for cargo delivery. Methods in Molecular Biology 298 Peptide Synthesis and Applications77–89 New York: Springer [Google Scholar]
  112. Frankel AD, Pabo CO. 112.  1988. Cellular uptake of the tat protein from human immunodeficiency virus. Cell 55:61189–93 [Google Scholar]
  113. Green M, Loewenstein PM. 113.  1988. Autonomous functional domains of chemically synthesized human immunodeficiency virus tat trans-activator protein. Cell 55:61179–88 [Google Scholar]
  114. Derossi D, Joliot AH, Chassaing G, Prochiantz A. 114.  1994. The third helix of the Antennapedia homeodomain translocates through biological membranes. J. Biol. Chem. 269:1410444–50 [Google Scholar]
  115. Lindgren M, Hallbrink M, Prochiantz A, Langel Ü. 115.  2000. Cell-penetrating peptides. Trends Pharm. Sci. 21:399–103 [Google Scholar]
  116. Derossi D, Calvet S, Trembleau A, Brunissen A, Chassaing G, Prochiantz A. 116.  1996. Cell internalization of the third helix of the Antennapedia homeodomain is receptor-independent. J. Biol. Chem. 271:3018188–93 [Google Scholar]
  117. Vives E, Brodin P, Lebleu B. 117.  1997. A truncated HIV-1 Tat protein basic domain rapidly translocates through the plasma membrane and accumulates in the cell nucleus. J. Biol. Chem. 272:2516010–17 [Google Scholar]
  118. Soomets U, Lindgren M, Gallet X, Hallbrink M, Elmquist A. 118.  et al. 2000. Deletion analogues of transportan. Biochim. Biophys. Acta 1467:1165–76 [Google Scholar]
  119. Farrera-Sinfreu J, Giralt E, Castel S, Albericio F, Royo M. 119.  2005. Cell-penetrating cis-γ-amino-l-proline-derived peptides. J. Am. Chem. Soc. 127:269459–68 [Google Scholar]
  120. Copolovici DM, Langel K, Eriste E, Langel Ü. 120.  2014. Cell-penetrating peptides: design, synthesis, and applications. ACS Nano 8:31972–94 [Google Scholar]
  121. Patel LN, Zaro JL, Shen WC. 121.  2007. Cell penetrating peptides: intracellular pathways and pharmaceutical perspectives. Pharm. Res. 24:111977–92 [Google Scholar]
  122. Stewart KM, Horton KL, Kelley SO. 122.  2008. Cell-penetrating peptides as delivery vehicles for biology and medicine. Org. Biomol. Chem. 6:132242–55 [Google Scholar]
  123. Johansson HJ, El-Andaloussi S, Holm T, Mäe M, Jänes J. 123.  et al. 2008. Characterization of a novel cytotoxic cell-penetrating peptide derived from p14ARF protein. Mol. Ther. 16:1115–23 [Google Scholar]
  124. Howl J, Matou-Nasri S, West DC, Farquhar M, Slaninova J. 124.  et al. 2012. Bioportide: an emergent concept of bioactive cell-penetrating peptides. Cell. Mol. Life Sci. 69:172951–66 [Google Scholar]
  125. Milne JC, Furlong D, Hanna PC, Wall JS, Collier RJ. 125.  1994. Anthrax protective antigen forms oligomers during intoxication of mammalian cells. J. Biol. Chem. 269:3220607–12 [Google Scholar]
  126. Pannifer AD, Wong TY, Schwarzenbacher R, Renatus M, Petosa C. 126.  et al. 2001. Crystal structure of the anthrax lethal factor. Nature 414:6860229–33 [Google Scholar]
  127. Liao X, Rabideau AE, Pentelute BL. 127.  2014. Delivery of antibody mimics into mammalian cells via anthrax toxin protective antigen. ChemBioChem 15:162458–66 [Google Scholar]
  128. Rabideau AE, Liao X, Akcay G, Pentelute BL. 128.  2015. Translocation of non-canonical polypeptides into cells using protective antigen. Sci. Rep. 5:11944 [Google Scholar]
  129. Swaminathan J, Ehrhardt C. 129.  2012. Liposomal delivery of proteins and peptides. Expert Opin. Drug Deliv. 9:121489–503 [Google Scholar]
  130. Immordino ML, Dosio F, Cattel L. 130.  2006. Stealth liposomes: review of the basic science, rationale, and clinical applications, existing and potential. Int. J. Nanomed. 1:3297–315 [Google Scholar]
  131. Desnick RJ, Thorpe SR, Fiddler MB. 131.  1976. Toward enzyme therapy for lysosomal storage diseases. Physiol. Rev. 56:157–99 [Google Scholar]
  132. Das PK, Murray GJ, Zirzow GC, Brady RO, Barranger JA. 132.  1985. Lectin-specific targeting of β-glucocerebrosidase to different liver cells via glycosylated liposomes. Biochem. Med. 33:1124–31 [Google Scholar]
  133. Allen TM. 133.  2002. Ligand-targeted therapeutics in anticancer therapy. Nat. Rev. Cancer 2:10750–63 [Google Scholar]
  134. Ye M, Kim S, Park K. 134.  2010. Issues in long-term protein delivery using biodegradable microparticles. J. Control. Release 146:2241–60 [Google Scholar]
  135. Shi Y, Li LC. 135.  2005. Current advances in sustained-release systems for parenteral drug delivery. Expert Opin. Drug Deliv. 2:61039–58 [Google Scholar]
  136. Sinha VR, Trehan A. 136.  2003. Biodegradable microspheres for protein delivery. J. Control. Release 90:3261–80 [Google Scholar]
  137. Marazuela EG, Prado N, Moro E, Fernández-García H, Villalba M. 137.  et al. 2008. Intranasal vaccination with poly(lactide-co-glycolide) microparticles containing a peptide T of Ole e 1 prevents mice against sensitization. Clin. Exp. Allergy 38:3520–28 [Google Scholar]
  138. Patel ZS, Yamamoto M, Ueda H, Tabata Y, Mikos AG. 138.  2008. Biodegradable gelatin microparticles as delivery systems for the controlled release of bone morphogenetic protein-2. Acta Biomater 4:51126–38 [Google Scholar]
  139. Li Z, Li L, Liu Y, Zhang H, Li X. 139.  et al. 2011. Development of interferon alpha-2b microspheres with constant release. Int. J. Pharm. 410:1–248–53 [Google Scholar]
  140. Degim IT, Celebi N. 140.  2007. Controlled delivery of peptides and proteins. Curr. Pharm. Des. 13:199–117 [Google Scholar]
  141. Hrkach J, von Hoff D, Mukkaram Ali M, Andrianova E, Auer J. 141.  et al. 2012. Preclinical development and clinical translation of a PSMA-targeted docetaxel nanoparticle with a differentiated pharmacological profile. Sci. Transl. Med. 4:128128ra39 [Google Scholar]
  142. Rahman MA, Amin AR, Wang X, Zuckerman JE, Choi CH. 142.  et al. 2012. Systemic delivery of siRNA nanoparticles targeting RRM2 suppresses head and neck tumor growth. J. Control. Release 159:3384–92 [Google Scholar]
  143. Li Y, Pei Y, Zhang X, Gu Z, Zhou Z. 143.  et al. 2001. PEGylated PLGA nanoparticles as protein carriers: synthesis, preparation and biodistribution in rats. J. Control. Release 71:2203–11 [Google Scholar]
  144. Sarmento B, Ribeiro A, Veiga F, Sampaio P, Neufeld R, Ferreira D. 144.  2007. Alginate/chitosan nanoparticles are effective for oral insulin delivery. Pharm. Res. 24:122198–2206 [Google Scholar]
  145. Tobio M, Sánchez A, Vila A, Soriano II, Evora C. 145.  et al. 2000. The role of PEG on the stability in digestive fluids and in vivo fate of PEG-PLA nanoparticles following oral administration. Colloids Surf. B Biointerfaces 18:3–4315–23 [Google Scholar]
  146. Mohanraj VJ, Barnes TJ, Prestidge CA. 146.  2010. Silica nanoparticle coated liposomes: a new type of hybrid nanocapsule for proteins. Int. J. Pharm. 392:1–2285–93 [Google Scholar]
  147. Cho YW, Park SA, Han TH, Son DH, Park JS. 147.  et al. 2007. In vivo tumor targeting and radionuclide imaging with self-assembled nanoparticles: mechanisms, key factors, and their implications. Biomaterials 28:61236–47 [Google Scholar]
  148. Li X, Min M, Du N, Gu Y, Hode T. 148.  et al. 2013. Chitin, chitosan, and glycated chitosan regulate immune responses: the novel adjuvants for cancer vaccine. Clin. Dev. Immunol 2013:387023 [Google Scholar]
  149. Kim JH, Kim YS, Park K, Kang E, Lee S. 149.  et al. 2008. Self-assembled glycol chitosan nanoparticles for the sustained and prolonged delivery of antiangiogenic small peptide drugs in cancer therapy. Biomaterials 29:121920–30 [Google Scholar]
  150. Park J, Wrzesinski SH, Stern E, Look M, Criscione J. 150.  et al. 2012. Combination delivery of TGF-β inhibitor and IL-2 by nanoscale liposomal polymeric gels enhances tumour immunotherapy. Nat. Mater. 11:10895–905 [Google Scholar]
  151. Cheng Q, Feng J, Chen J, Zhu X, Li F. 151.  2008. Brain transport of neurotoxin-I with PLA nanoparticles through intranasal administration in rats: a microdialysis study. Biopharm. Drug Dispos. 29:8431–39 [Google Scholar]
  152. Ando Y, Kumar M. 152.  2010. A special issue on carbon nanotubes. There's plenty of room at the bottom... in the CNT basement strengthen the foundation before erecting the sky-tower. J. Nanosci. Nanotechnol. 10:63723–25 [Google Scholar]
  153. Cholkar K, Patel A, Vadlapudi AD, Mitra AK. 153.  2012. Novel nanomicellar formulation approaches for anterior and posterior segment ocular drug delivery. Recent Patents Nanomed 2:282–95 [Google Scholar]
  154. Shi Y, Huang W, Liang R, Sun K, Zhang F. 154.  et al. 2013. Improvement of in vivo efficacy of recombinant human erythropoietin by encapsulation in PEG–PLA micelle. Int. J. Nanomed. 8:1–11 [Google Scholar]
  155. Lim SB, Rubinstein I, Önyüksel H. 155.  2008. Freeze drying of peptide drugs self-associated with long-circulating, biocompatible and biodegradable sterically stabilized phospholipid nanomicelles. Int. J. Pharm. 356:1–2345–50 [Google Scholar]
  156. Banerjee A, Önyüksel H. 156.  2012. Peptide delivery using phospholipid micelles. WIREs Nanomed. Nanobiotechnol 4:5562–74 [Google Scholar]
  157. Lim SB, Rubinstein I, Sadikot RT, Artwohl JE, Önyüksel H. 157.  2011. A novel peptide nanomedicine against acute lung injury: GLP-1 in phospholipid micelles. Pharm. Res. 28:3662–72 [Google Scholar]
/content/journals/10.1146/annurev-pharmtox-010716-104805
Loading
/content/journals/10.1146/annurev-pharmtox-010716-104805
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error