What affects the rate of diffusion across the membrane and what affects membrane permeability?

1. Stein WD, Lieb WR. Transport and diffusion across cell membranes. 1st. Orlando, FL: Academic; 1986. [Google Scholar]

2. Alberts B, Johnson A, Lewis J, et al. Molecular biology of the cell. 5th. New York: Garland Science; 2007. [Google Scholar]

3. Di L, Artursson P, Avdeef A, et al. Evidence-based approach to assess passive diffusion and carrier-mediated drug transport. Drug Discov Today. 2012;17:905–912. [PubMed] [Google Scholar]

4. Engelman DM. Membranes are more mosaic than fluid. Nature. 2005;438:578–580. [PubMed] [Google Scholar]

5. Jacobson K, Mouritsen OG, Anderson RGW. Lipid rafts: at a crossroad between cell biology and physics. Nat Cell Biol. 2007;9:7–14. [PubMed] [Google Scholar]

6. Koichi K, Michiya F, Makoto N. Lipid components of two different regions of an intestinal epithelial cell membrane of mouse. Biochim Biophys Acta. 1974;369:222–233. [PubMed] [Google Scholar]

7. Marsh D, Horváth LI. Structure, dynamics and composition of the lipid-protein interface. Perspectives from spin-labelling. Biochim Biophys Acta. 1998;1376:267–296. [PubMed] [Google Scholar]

8. Lee AG. Lipid-protein interactions in biological membranes: a structural perspective. Biochim Biophys Acta. 2003;1612:1–40. [PubMed] [Google Scholar]

9. Zachowski A. Phospholipids in animal eukaryotic membranes: transverse asymmetry and movement. Biochem J. 1993;294:1–14. [PMC free article] [PubMed] [Google Scholar]

10. Leventis R, Silvius JR. Use of cyclodextrins to monitor transbilayer movement and differential lipid affinities of cholesterol. Biophys J. 2001;81:2257–2267. [PMC free article] [PubMed] [Google Scholar]

11. Steck TL, Ye J, Lange Y. Probing red cell membrane cholesterol movement with cyclodextrin. Biophys J. 2002;83:2118–2125. [PMC free article] [PubMed] [Google Scholar]

12. Conner SD, Schmid SL. Regulated portals of entry into the cell. Nature. 2003;422:37–44. [PubMed] [Google Scholar]

13. Mercer J, Helenius A. Virus entry by macropinocytosis. Nat Cell Biol. 2009;11:510–520. [PubMed] [Google Scholar]

14. Alberts B, Johnson A, Lewis J, et al. [Accessed 27 Feb 2014];Molecular biology of the cell. 2002 http://www.ncbi.nlm.nih.gov/books/NBK21054/

15. Orsi M, Essex JW. Passive permeation across lipid bilayers: a literature review. Molecular simulations and biomembranes: from biophysics to function. 2010:76–90. [Google Scholar]

16. Kansy M, Senner F, Gubernator K. Physicochemical high throughput screening: parallel artificial membrane permeation assay in the description of passive absorption processes. J Med Chem. 1998;41:1007–1010. [PubMed] [Google Scholar]

17. Sugano K, Kansy M, Artursson P, et al. Coexistence of passive and carrier-mediated processes in drug transport. Nat Rev Drug Discov. 2010;9:597–614. [PubMed] [Google Scholar]

18. Di L, Whitney-Pickett C, Umland JP, et al. Development of a new permeability assay using low-efflux MDCKII cells. J Pharm Sci. 2011;100:4974–4985. [PubMed] [Google Scholar]

19. Shamu CE, Story CM, Rapoport TA, Ploegh HL. The pathway of Us11-dependent degradation of Mhc class I heavy chains involves a ubiquitin-conjugated intermediate. J Cell Biol. 1999;147:45–58. [PMC free article] [PubMed] [Google Scholar]

20. Bartz R, Fan H, Zhang J, et al. Effective siRNA delivery and target mRNA degradation using an amphipathic peptide to facilitate pH-dependent endosomal escape. Biochem J. 2011;435:475–487. [PubMed] [Google Scholar]

21. Bittner MA, Holz RW. Effects of tetanus toxin on catecholamine release from intact and digitonin-permeabilized chromaffin cells. J Neurochem. 1988;51:451–456. [PubMed] [Google Scholar]

22. Moellering RE, Cornejo M, Davis TN, et al. Direct inhibition of the NOTCH transcription factor complex. Nature. 2009;462:182–188. [PMC free article] [PubMed] [Google Scholar]

23. Chang YS, Graves B, Guerlavais V, et al. Stapled α-helical peptide drug development: a potent dual inhibitor of MDM2 and MDMX for p53-dependent cancer therapy. Proc Natl Acad Sci. 2013;110:E3445–E3454. [PMC free article] [PubMed] [Google Scholar]

24. Bonner DK, Leung C, Chen-Liang J, et al. Intracellular trafficking of polyamido-amine-poly(ethylene glycol) block copolymers in DNA delivery. Bioconjug Chem. 2011;22:1519–1525. [PMC free article] [PubMed] [Google Scholar]

25. Richard JP, Melikov K, Vives E, et al. Cell-penetrating peptides. A reevaluation of the mechanism of cellular uptake. J Biol Chem. 2003;278:585–590. [PubMed] [Google Scholar]

26. Bechara C, Sagan S. Cell-penetrating peptides: 20 years later, where do we stand? FEBS Lett. 2013;587:1693–1702. [PubMed] [Google Scholar]

27. Cebrian I, Visentin G, Blanchard N, et al. Sec22b regulates phagosomal maturation and antigen crosspresentation by dendritic cells. Cell. 2011;147:1355–1368. [PubMed] [Google Scholar]

28. Yu P, Liu B, Kodadek T. A high-throughput assay for assessing the cell permeability of combinatorial libraries. Nat Biotechnol. 2005;23:746–751. [PubMed] [Google Scholar]

29. Holub JM, LaRochelle JR, Appelbaum JS, Schepartz A. Improved assays for determining the cytosolic access of peptides, proteins, and their mimetics. Biochemistry (Mosc) 2013;52:9036–9046. [PMC free article] [PubMed] [Google Scholar]

30. Zlokarnik G, Negulescu PA, Knapp TE, et al. Quantitation of transcription and clonal selection of single living cells with β-lactamase as reporter. Science. 1998;279:84–88. [PubMed] [Google Scholar]

31. Bordonaro M. Modular Cre/lox system and genetic therapeutics for colorectal cancer. J Biomed Biotechnol. 2009 [PMC free article] [PubMed] [Google Scholar]

32. Yamaizumi M, Mekada E, Uchida T, Okada Y. One molecule of diphtheria toxin fragment a introduced into a cell can kill the cell. Cell. 1978;15:245–250. [PubMed] [Google Scholar]

33. Eiklid K, Olsnes S, Pihl A. Entry of lethal doses of abrin, ricin and modeccin into the cytosol of HeLa cells. Exp Cell Res. 1980;126:321–326. [PubMed] [Google Scholar]

34. Diamond JM, Katz Y. Interpretation of nonelectrolyte partition coefficients between dimyristoyl lecithin and water. J Membr Biol. 1974;17:121–154. [PubMed] [Google Scholar]

35. Finkelstein A. Water and nonelectrolyte permeability of lipid bilayer membranes. J Gen Physiol. 1976;68:127–135. [PMC free article] [PubMed] [Google Scholar]

36. Subczynski WK, Hyde JS, Kusumi A. Oxygen permeability of phosphatidylcholine- cholesterol membranes. Proc Natl Acad Sci. 1989;86:4474–4478. [PMC free article] [PubMed] [Google Scholar]

37. Gutknecht J, Bisson MA, Tosteson FC. Diffusion of carbon dioxide through lipid bilayer membranes: effects of carbonic anhydrase, bicarbonate, and unstirred layers. J Gen Physiol. 1977;69:779–794. [PMC free article] [PubMed] [Google Scholar]

38. Walter A, Gutknecht J. Permeability of small nonelectrolytes through lipid bilayer membranes. J Membr Biol. 1986;90:207–217. [PubMed] [Google Scholar]

39. Orbach E, Finkelstein A. The nonelectrolyte permeability of planar lipid bilayer membranes. J Gen Physiol. 1980;75:427–436. [PMC free article] [PubMed] [Google Scholar]

40. Papahadjopoulos D, Nir S, Oki S. Permeability properties of phospholipid membranes: effect of cholesterol and temperature. Biochim Biophys Acta. 1972;266:561–583. [PubMed] [Google Scholar]

41. Mendel CM. The free hormone hypothesis: a physiologically based mathematical model. Endocr Rev. 1989;10:232–274. [PubMed] [Google Scholar]

42. Giorgi EP, Stein WD. The transport of steroids into animal cells in culture. Endocrinology. 1981;108:688–697. [PubMed] [Google Scholar]

43. Bockus AT, McEwen CM, Lokey RS. Form and function in cyclic peptide natural products: a pharmacokinetic perspective. Curr Top Med Chem. 2013;13:821–836. [PubMed] [Google Scholar]

44. Augustijns PF, Bradshaw TP, Gan LSL, et al. Evidence for a polarized efflux system in Caco-2 cells capable of modulating cyclosporine A transport. Biochem Biophys Res Commun. 1993;197:360–365. [PubMed] [Google Scholar]

45. Rezai T, Bock JE, Zhou MV, et al. Conformational flexibility, internal hydrogen bonding, and passive membrane permeability: successful in silico prediction of the relative permeabilities of cyclic peptides. J Am Chem Soc. 2006;128:14073–14080. [PubMed] [Google Scholar]

46. Guimarães CRW, Mathiowetz AM, Shalaeva M, et al. Use of 3D properties to characterize beyond rule-of-5 property space for passive permeation. J Chem Inf Model. 2012;52:882–890. [PubMed] [Google Scholar]

47. Hediger MA, Clémençon B, Burrier RE, Bruford EA. The ABCs of membrane transporters in health and disease (SLC series): introduction. Mol Aspects Med. 2013;34:95–107. [PMC free article] [PubMed] [Google Scholar]

48. Saier MH, Reddy VS, Tamang DG, Vastermark A. The transporter classification database. Nucleic Acids Res. 2013;42:D251–D258. [PMC free article] [PubMed] [Google Scholar]

49. Hediger MA. The ABCs of membrane transporters in health and disease (SLC series) Mol Aspects Med. 2013;34(2–3):95–752. [PMC free article] [PubMed] [Google Scholar]

50. Kew JNC, Davies CH. Ion channels: from structure to function. Oxford: Oxford University Press; 2010. [Google Scholar]

51. Enyedi P, Czirják G. Molecular background of leak K+ currents: two-pore domain potassium channels. Physiol Rev. 2010;90:559–605. [PubMed] [Google Scholar]

52. Toyoshima C, Kanai R, Cornelius F. First crystal structures of Na+, K+-ATPase: new light on the oldest ion pump. Structure. 2011;19:1732–1738. [PubMed] [Google Scholar]

53. Duax WL, Griffin JF, Langs DA, et al. Molecular structure and mechanisms of action of cyclic and linear ion transport antibiotics. Pept Sci. 1996;40:141–155. [PubMed] [Google Scholar]

54. Wallace BA. Recent advances in the high resolution structures of bacterial channels: gramicidin A. J Struct Biol. 1998;121:123–141. [PubMed] [Google Scholar]

55. Zheng L, Kostrewa D, Bernèche S, et al. The mechanism of ammonia transport based on the crystal structure of AmtB of Escherichia coli. Proc Natl Acad Sci U S A. 2004;101:17090–17095. [PMC free article] [PubMed] [Google Scholar]

56. Andrade SLA, Einsle O. The Amt/Mep/Rh family of ammonium transport proteins. Mol Membr Biol. 2007;24:357–365. [PubMed] [Google Scholar]

57. Shayakul C, Clémençon B, Hediger MA. The urea transporter family (SLC14): physiological, pathological and structural aspects. Mol Aspects Med. 2013;34:313–322. [PubMed] [Google Scholar]

58. Ishibashi K, Hara S, Kondo S. Aquaporin water channels in mammals. Clin Exp Nephrol. 2009;13:107–117. [PubMed] [Google Scholar]

59. Bienert GP, Chaumont F. Aquaporin-facilitated transmembrane diffusion of hydrogen peroxide. Biochim Biophys Acta. 2013 [PubMed] [Google Scholar]

60. Mueckler M, Thorens B. The SLC2 (GLUT) family of membrane transporters. Mol Aspects Med. 2013;34:121–138. [PMC free article] [PubMed] [Google Scholar]

61. Schweikhard ES, Ziegler CM. Amino acid secondary transporters: toward a common transport mechanism. Curr Top Membr. 2012;70:1–28. [PubMed] [Google Scholar]

62. Young JD, Yao SYM, Baldwin JM, et al. The human concentrative and equilibrative nucleoside transporter families, SLC28 and SLC29. Mol Aspects Med. 2013;34:529–547. [PubMed] [Google Scholar]

63. Smith DE, Clémençon B, Hediger MA. Proton-coupled oligopeptide transporter family SLC15: physiological, pharmacological and pathological implications. Mol Aspects Med. 2013;34:323–336. [PMC free article] [PubMed] [Google Scholar]

64. Letschert K, Faulstich H, Keller D, Keppler D. Molecular characterization and inhibition of amanitin uptake into human hepatocytes. Toxicol Sci. 2006;91:140–149. [PubMed] [Google Scholar]

65. Chen Z-S, Tiwari AK. Multidrug resistance proteins (MRPs/ABCCs) in cancer chemotherapy and genetic diseases. FEBS J. 2011;278:3226–3245. [PMC free article] [PubMed] [Google Scholar]

66. Amin ML. P-glycoprotein inhibition for optimal drug delivery. Drug Target Insights. 2013;7:27–34. [PMC free article] [PubMed] [Google Scholar]

67. Natarajan K, Xie Y, Baer MR, Ross DD. Role of breast cancer resistance protein (BCRP/ABCG2) in cancer drug resistance. Biochem Pharmacol. 2012;83:1084–1103. [PMC free article] [PubMed] [Google Scholar]

68. Langel U. Handbook of cell-penetrating peptides. 2nd. Boca Raton: CRC Press; 2010. [Google Scholar]

69. Sagan S, Burlina F, Alves ID, et al. Homeoproteins and homeoprotein-derived peptides: going in and out. Curr Pharm Des. 2013;19:2851–2862. [PubMed] [Google Scholar]

70. Schmidt N, Mishra A, Lai GH, Wong GCL. Arginine-rich cell-penetrating peptides. FEBS Lett. 2010;584:1806–1813. [PubMed] [Google Scholar]

71. Futaki S, Hirose H, Nakase I. Arginine-rich peptides: methods of translocation through biological membranes. Curr Pharm Des. 2013;19:2863–2868. [PubMed] [Google Scholar]

72. Tyagi M, Rusnati M, Presta M, Giacca M. Internalization of HIV-1 Tat requires cell surface heparan sulfate proteoglycans. J Biol Chem. 2001;276:3254–3261. [PubMed] [Google Scholar]

73. Su Y, Waring AJ, Ruchala P, Hong M. Membrane-bound dynamic structure of an arginine-rich cell-penetrating peptide, the protein transduction domain of HIV TAT, from solid-state NMR. Biochemistry (Mosc) 2010;49:6009–6020. [PMC free article] [PubMed] [Google Scholar]

74. Wadia JS, Stan RV, Dowdy SF. Transducible TAT-HA fusogenic peptide enhances escape of TAT-fusion proteins after lipid raft macropinocytosis. Nat Med. 2004;10:310–315. [PubMed] [Google Scholar]

75. Nakase I, Tadokoro A, Kawabata N, et al. Interaction of arginine-rich peptides with membrane-associated proteoglycans is crucial for induction of actin organization and macropinocytosis. Biochemistry (Mosc) 2007;46:492–501. [PubMed] [Google Scholar]

76. Yesylevskyy S, Marrink S-J, Mark AE. Alternative mechanisms for the interaction of the cell-penetrating peptides penetratin and the TAT peptide with lipid bilayers. Biophys J. 2009;97:40–49. [PMC free article] [PubMed] [Google Scholar]

77. Herce HD, Garcia AE, Litt J, et al. Arginine-rich peptides destabilize the plasma membrane, consistent with a pore formation translocation mechanism of cell-penetrating peptides. Biophys J. 2009;97:1917–1925. [PMC free article] [PubMed] [Google Scholar]

78. Mishra A, Lai GH, Schmidt NW, et al. Translocation of HIV TAT peptide and analogues induced by multiplexed membrane and cytoskeletal interactions. Proc Natl Acad Sci. 2011;108:16883–16888. [PMC free article] [PubMed] [Google Scholar]

79. Kawamoto S, Miyakawa T, Takasu M, et al. Cell-penetrating peptide induces various deformations of lipid bilayer membrane: inverted micelle, double bilayer, and trans-membrane. Int J Quantum Chem. 2012;112:178–183. [Google Scholar]

80. Huang K, García AE. Free energy of translocating an arginine-rich cell-penetrating peptide across a lipid bilayer suggests pore formation. Biophys J. 2013;104:412–420. [PMC free article] [PubMed] [Google Scholar]

81. Jones S, Howl J. Enantiomer-specific bioactivities of peptidomimetic analogues of mastoparan and mitoparan: characterization of inverso mastoparan as a highly efficient cell penetrating peptide. Bioconjug Chem. 2012;23:47–56. [PubMed] [Google Scholar]

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

83. Foerg C, Merkle HP. On the biomedical promise of cell penetrating peptides: limits versus prospects. J Pharm Sci. 2008;97:144–162. [PubMed] [Google Scholar]

84. Sandvig K, van Deurs B. Delivery into cells: lessons learned from plant and bacterial toxins. Gene Ther. 2005;12:865–872. [PubMed] [Google Scholar]

85. Falnes PØ, Sandvig K. Penetration of protein toxins into cells. Curr Opin Cell Biol. 2000;12:407–413. [PubMed] [Google Scholar]

86. Collier RJ. Membrane translocation by anthrax toxin. Mol Aspects Med. 2009;30:413–422. [PMC free article] [PubMed] [Google Scholar]

87. De Virgilio M, Lombardi A, Caliandro R, Fabbrini MS. Ribosome-inactivating proteins: from plant defense to tumor attack. Toxins. 2010;2:2699–2737. [PMC free article] [PubMed] [Google Scholar]

88. Spooner RA, Lord JM. How ricin and shiga toxin reach the cytosol of target cells: retrotranslocation from the endoplasmic reticulum. In: Mantis N, editor. Ricin shiga toxins. Berlin: Springer; 2012. pp. 19–40. [PubMed] [Google Scholar]

89. Sandvig K, Skotland T, van Deurs B, Klokk TI. Retrograde transport of protein toxins through the Golgi apparatus. Histochem Cell Biol. 2013;140:317–326. [PubMed] [Google Scholar]

90. Wernick NLB, Chinnapen DJ-F, Cho JA, Lencer WI. Cholera toxin: an intracellular journey into the cytosol by way of the endoplasmic reticulum. Toxins. 2010;2:310–325. [PMC free article] [PubMed] [Google Scholar]

91. Cho JA, Chinnapen DJ-F, Aamar E, et al. Insights on the trafficking and retro-translocation of glycosphingolipid-binding bacterial toxins. Front Cell Infect Microbiol. 2012 [PMC free article] [PubMed] [Google Scholar]

92. Mercer J, Schelhaas M, Helenius A. Virus entry by endocytosis. Annu Rev Biochem. 2010;79:803–833. [PubMed] [Google Scholar]

93. Sriwilaijaroen N, Suzuki Y. Molecular basis of the structure and function of H1 hemagglutinin of influenza virus. Proc Jpn Acad Ser B Phys Biol Sci. 2012;88:226–249. [PMC free article] [PubMed] [Google Scholar]

94. Tsai B. Penetration of nonenveloped viruses into the cytoplasm. Annu Rev Cell Dev Biol. 2007;23:23–43. [PubMed] [Google Scholar]

95. Johnson J, Banerjee M. Activation, exposure and penetration of virally encoded, membrane-active polypeptides during non-enveloped virus entry. Curr Protein Pept Sci. 2008;9:16–27. [PubMed] [Google Scholar]

96. Moyer CL, Nemerow GR. Viral weapons of membrane destruction: variable modes of membrane penetration by non-enveloped viruses. Curr Opin Virol. 2011;1:44–99. [PMC free article] [PubMed] [Google Scholar]

97. Inoue T, Tsai B. How viruses use the endoplasmic reticulum for entry, replication, and assembly. Cold Spring Harb Perspect Biol. 2013;5:a013250. [PMC free article] [PubMed] [Google Scholar]

98. Suomalainen M, Greber UF. Uncoating of non-enveloped viruses. Curr Opin Virol. 2013;3:27–33. [PubMed] [Google Scholar]

99. Veber DF, Johnson SR, Cheng H-Y, et al. Molecular properties that influence the oral bioavailability of drug candidates. J Med Chem. 2002;45:2615–2623. [PubMed] [Google Scholar]

100. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev. 1997;23:3–25. [PubMed] [Google Scholar]

101. Faller B, Ottaviani G, Ertl P, et al. Evolution of the physicochemical properties of marketed drugs: can history foretell the future? Drug Discov Today. 2011;16:976–984. [PubMed] [Google Scholar]

102. Ertl P, Rohde B, Selzer P. Fast calculation of molecular polar surface area as a sum of fragment-based contributions and its application to the prediction of drug transport properties. J Med Chem. 2000;43:3714–3717. [PubMed] [Google Scholar]

103. Xiang T-X, Anderson BD. Influence of chain ordering on the selectivity of dipalmi-toylphosphatidylcholine bilayer membranes for permeant size and shape. Biophys J. 1998;75:2658–2671. [PMC free article] [PubMed] [Google Scholar]

104. Kuhn B, Mohr P, Stahl M. Intramolecular hydrogen bonding in medicinal chemistry. J Med Chem. 2010;53:2601–2611. [PubMed] [Google Scholar]

105. Mayer PT, Xiang T-X, Anderson BD. Independence of substituent contributions to the transport of small-molecule permeants in lipid bilayer. AAPS Pharm Sci. 2000;2:40–52. [PMC free article] [PubMed] [Google Scholar]

106. Ulander J, Haymet ADJ. Permeation across hydrated DPPC lipid bilayers: simulation of the titrable amphiphilic drug valproic acid. Biophys J. 2003;85:3475–3484. [PMC free article] [PubMed] [Google Scholar]

107. Xiang T-X, Anderson BD. Liposomal drug transport: a molecular perspective from molecular dynamics simulations in lipid bilayers. Adv Drug Deliv Rev. 2006;58:1357–1378. [PubMed] [Google Scholar]

108. Bennett WFD, MacCallum JL, Hinner MJ, et al. Molecular view of cholesterol flip-flop and chemical potential in different membrane environments. J Am Chem Soc. 2009;131:12714–12720. [PubMed] [Google Scholar]

109. Maeda K, Sugiyama Y. Transporter biology in drug approval: regulatory aspects. Mol Aspects Med. 2013;34:711–718. [PubMed] [Google Scholar]

110. Dobson PD, Patel Y, Kell DB. “Metabolite-likeness” as a criterion in the design and selection of pharmaceutical drug libraries. Drug Discov Today. 2009;14:31–40. [PubMed] [Google Scholar]

111. Dahan A, Khamis M, Agbaria R, Karaman R. Targeted prodrugs in oral drug delivery: the modern molecular biopharmaceutical approach. Expert Opin Drug Deliv. 2012;9:1001–1013. [PubMed] [Google Scholar]

112. Majumdar S, Duvvuri S, Mitra AK. Membrane transporter/receptor-targeted prodrug design: strategies for human and veterinary drug development. Adv Drug Deliv Rev. 2004;56:1437–1452. [PubMed] [Google Scholar]

113. Keppler A, Arrivoli C, Sironi L, Ellenberg J. Fluorophores for live cell imaging of AGT fusion proteins across the visible spectrum. Biotechniques. 2006;41:167–170. 172, 174–175. [PubMed] [Google Scholar]

114. Tsien RY. A non-disruptive technique for loading calcium buffers and indicators into cells. Nature. 1981;290:527–528. [PubMed] [Google Scholar]

115. Ries RS, Choi H, Blunck R, et al. Black lipid membranes: visualizing the structure, dynamics, and substrate dependence of membranes. J Phys Chem B. 2004;108:16040–16049. [Google Scholar]

116. Melikyan GB, Deriy BN, Ok DC, Cohen FS. Voltage-dependent translocation of R18 and DiI across lipid bilayers leads to fluorescence changes. Biophys J. 1996;71:2680–2691. [PMC free article] [PubMed] [Google Scholar]

117. Kleinfeld AM, Chu P, Storch J. Flip-flop is slow and rate limiting for the movement of long chain anthroyloxy fatty acids across lipid vesicles. Biochemistry (Mosc) 1997;36:5702–5711. [PubMed] [Google Scholar]

118. Homolya L, Holló Z, Germann UA, et al. Fluorescent cellular indicators are extruded by the multidrug resistance protein. J Biol Chem. 1993;268:21493–21496. [PubMed] [Google Scholar]

119. Chidley C, Haruki H, Pedersen MG, et al. A yeast-based screen reveals that sulfasalazine inhibits tetrahydrobiopterin biosynthesis. Nat Chem Biol. 2011;7:375–383. [PubMed] [Google Scholar]

120. Driggers EM, Hale SP, Lee J, Terrett NK. The exploration of macrocycles for drug discovery—an underexploited structural class. Nat Rev Drug Discov. 2008;7:608–624. [PubMed] [Google Scholar]

121. Giordanetto F, Revell JD, Knerr L, et al. Stapled vasoactive intestinal peptide (VIP) derivatives improve VPAC2 agonism and glucose-dependent insulin secretion. ACS Med Chem Lett. 2013;4:1163–1168. [PMC free article] [PubMed] [Google Scholar]

122. Bock JE, Gavenonis J, Kritzer JA. Getting in shape: controlling peptide bioactivity and bioavailability using conformational constraints. ACS Chem Biol. 2013;8:488–499. [PMC free article] [PubMed] [Google Scholar]

123. Kwon Y-U, Kodadek T. Quantitative comparison of the relative cell permeability of cyclic and linear peptides. Chem Biol. 2007;14:671–677. [PubMed] [Google Scholar]

124. White TR, Renzelman CM, Rand AC, et al. On-resin N-methylation of cyclic peptides for discovery of orally bioavailable scaffolds. Nat Chem Biol. 2011;7:810–817. [PMC free article] [PubMed] [Google Scholar]

125. Malakoutikhah M, Prades R, Teixidó M, Giralt E. N-methyl phenylalanine-rich peptides as highly versatile blood-brain barrier shuttles. J Med Chem. 2010;53:2354–2363. [PubMed] [Google Scholar]

126. Ovadia O, Greenberg S, Chatterjee J, et al. The effect of multiple N-methylation on intestinal permeability of cyclic hexapeptides. Mol Pharm. 2011;8:479–487. [PubMed] [Google Scholar]

127. Azzarito V, Long K, Murphy NS, Wilson AJ. Inhibition of α-helix-mediated protein- protein interactions using designed molecules. Nat Chem. 2013;5:161–173. [PubMed] [Google Scholar]

128. Kim Y-W, Grossmann TN, Verdine GL. Synthesis of all-hydrocarbon stapled α-helical peptides by ring-closing olefin metathesis. Nat Protoc. 2011;6:761–771. [PubMed] [Google Scholar]

129. Patgiri A, Menzenski MZ, Mahon AB, Arora PS. Solid-phase synthesis of short α-helices stabilized by the hydrogen bond surrogate approach. Nat Protoc. 2010;5:1857–1865. [PMC free article] [PubMed] [Google Scholar]

130. Miller SE, Kallenbach NR, Arora PS. Reversible alpha-helix formation controlled by a hydrogen bond surrogate. Tetrahedron. 2012;68:4434–4437. [PMC free article] [PubMed] [Google Scholar]

131. Patgiri A, Yadav KK, Arora PS, Bar-Sagi D. An orthosteric inhibitor of the Ras-Sos interaction. Nat Chem Biol. 2011;7:585–587. [PMC free article] [PubMed] [Google Scholar]

132. Okamoto T, Zobel K, Fedorova A, et al. Stabilizing the pro-apoptotic BimBH3 Helix (BimSAHB) does not necessarily enhance affinity or biological activity. ACS Chem Biol. 2013;8:297–302. [PubMed] [Google Scholar]

133. Bird GH, Gavathiotis E, LaBelle JL, et al. Distinct BimBH3 (BimSAHB) stapled peptides for structural and cellular studies. ACS Chem Biol. 2014;9:831–837. [PMC free article] [PubMed] [Google Scholar]

134. Okamoto T, Segal D, Zobel K, et al. Further insights into the effects of pre-organizing the BimBH3 helix. ACS Chem Biol. 2014;9:838–839. [PubMed] [Google Scholar]

135. Verdine GL, Hilinski GJ. Stapled pep-tides for intracellular drug targets. In: Dane Wittrup K, Verdine GL, editors. Methods enzymol. New York: Academic; 2012. pp. 3–33. [PubMed] [Google Scholar]

136. Bird GH, Christian Crannell W, Walensky LD. Chemical synthesis of hydrocarbon-stapled peptides for protein interaction research and therapeutic targeting. Curr Protoc Chem Biol. 2011;3(3):99–117. [PMC free article] [PubMed] [Google Scholar]

137. Milletti F. Cell-penetrating peptides: classes, origin, and current landscape. Drug Discov Today. 2012;17:850–860. [PubMed] [Google Scholar]

138. Copolovici DM, Langel K, Eriste E, Langel U. Cell-penetrating peptides: design synthesis and applications. ACS Nano. 2014 [PubMed] [Google Scholar]

139. Appelbaum JS, LaRochelle JR, Smith BA, et al. Arginine topology controls escape of minimally cationic proteins from early endosomes to the cytoplasm. Chem Biol. 2012;19:819–830. [PMC free article] [PubMed] [Google Scholar]

140. Marschall ALJ, Frenzel A, Schirrmann T, et al. Targeting antibodies to the cytoplasm. mAbs. 2011;3:3–16. [PMC free article] [PubMed] [Google Scholar]

141. Gu Z, Biswas A, Zhao M, Tang Y. Tailoring nanocarriers for intracellular protein delivery. Chem Soc Rev. 2011;40:3638–3655. [PubMed] [Google Scholar]

142. Du J, Jin J, Yan M, Lu Y. Synthetic nanocarriers for intracellular protein delivery. Curr Drug Metab. 2012;13:82–92. [PubMed] [Google Scholar]

143. Salmaso S, Caliceti P. Self assembling nanocomposites for protein delivery: supra-molecular interactions of soluble polymers with protein drugs. Int J Pharm. 2013;440:111–123. [PubMed] [Google Scholar]

144. Zhang Y, Yu L-C. Microinjection as a tool of mechanical delivery. Curr Opin Biotechnol. 2008;19:506–510. [PubMed] [Google Scholar]

145. Sharei A, Zoldan J, Adamo A, et al. A vector-free microfluidic platform for intracellular delivery. Proc Natl Acad Sci. 2013;110:2082–2087. [PMC free article] [PubMed] [Google Scholar]

146. Shalek AK, Robinson JT, Karp ES, et al. Vertical silicon nanowires as a universal platform for delivering biomolecules into living cells. Proc Natl Acad Sci. 2010;107:1870–1875. [PMC free article] [PubMed] [Google Scholar]

147. Yosef N, Shalek AK, Gaublomme JT, et al. Dynamic regulatory network controlling TH17 cell differentiation. Nature. 2013;496:461–468. [PMC free article] [PubMed] [Google Scholar]

148. Lo SL, Wang S. Peptide-based nano-carriers for intracellular delivery of biologically active proteins. Organelle-specific pharmaceutical nanotechnology. 2010:323–336. [Google Scholar]

149. Koren E, Torchilin VP. Cell-penetrating peptides: breaking through to the other side. Trends Mol Med. 2012;18:385–393. [PubMed] [Google Scholar]

150. Nakase I, Tanaka G, Futaki S. Cell-penetrating peptides (CPPs) as a vector for the delivery of siRNAs into cells. Mol Biosyst. 2013;9:855–861. [PubMed] [Google Scholar]

151. Fawell S, Seery J, Daikh Y, et al. Tat-mediated delivery of heterologous proteins into cells. Proc Natl Acad Sci. 1994;91:664–668. [PMC free article] [PubMed] [Google Scholar]

152. Nagahara H, Vocero-Akbani AM, Snyder EL, et al. Transduction of full-length TAT fusion proteins into mammalian cells: TAT-p27Kip1 induces cell migration. Nat Med. 1998;4:1449–1452. [PubMed] [Google Scholar]

153. Morris MC, Depollier J, Mery J, et al. A peptide carrier for the delivery of biologically active proteins into mammalian cells. Nat Biotechnol. 2001;19:1173–1176. [PubMed] [Google Scholar]

154. Harford-Wright E, Lewis KM, Vink R, Ghabriel MN. Evaluating the role of substance P in the growth of brain tumors. Neuroscience. 2014;261:85–94. [PubMed] [Google Scholar]

155. Rizk SS, Luchniak A, Uysal S, et al. An engineered substance P variant for receptor-mediated delivery of synthetic antibodies into tumor cells. Proc Natl Acad Sci. 2009;106:11011–11015. [PMC free article] [PubMed] [Google Scholar]

156. Rizk SS, Misiura A, Paduch M, Kossiakoff AA. Substance P derivatives as versatile tools for specific delivery of various types of biomolecular cargo. Bioconjug Chem. 2011;23:42–46. [PMC free article] [PubMed] [Google Scholar]

157. Chatterjee S, Chaudhury S, McShan AC, et al. Structure and biophysics of type III secretion in bacteria. Biochemistry (Mosc) 2013;52:2508–2517. [PMC free article] [PubMed] [Google Scholar]

158. Carleton HA, Lara-Tejero M, Liu X, Galán JE. Engineering the type III secretion system in non-replicating bacterial minicells for antigen delivery. Nat Commun. 2013;4:1590. [PMC free article] [PubMed] [Google Scholar]

159. Doerner JF, Febvay S, Clapham DE. Controlled delivery of bioactive molecules into live cells using the bacterial mechanosensitive channel MscL. Nat Commun. 2012;3:990. [PMC free article] [PubMed] [Google Scholar]

160. Dunstone MA, Tweten RK. Packing a punch: the mechanism of pore formation by cholesterol dependent cytolysins and membrane attack complex/perforin-like proteins. Curr Opin Struct Biol. 2012;22:342–349. [PMC free article] [PubMed] [Google Scholar]

161. Provoda CJ, Stier EM, Lee K-D. Tumor cell killing enabled by listeriolysin O-liposome-mediated delivery of the protein toxin gelonin. J Biol Chem. 2003;278:35102–35108. [PubMed] [Google Scholar]

162. Pirie CM, Liu DV, Wittrup KD. Targeted cytolysins synergistically potentiate cytoplasmic delivery of gelonin immunotoxin. Mol Cancer Ther. 2013;12:1774–1782. [PMC free article] [PubMed] [Google Scholar]

163. Sandvig K, van Deurs B. Membrane traffic exploited by protein toxins. Annu Rev Cell Dev Biol. 2002;18:1–24. [PubMed] [Google Scholar]

164. Johannes L, Römer W. Shiga toxins— from cell biology to biomedical applications. Nat Rev Microbiol. 2010;8:105–116. [PubMed] [Google Scholar]

165. Pastan I, Hassan R, FitzGerald DJ, Kreitman RJ. Immunotoxin treatment of cancer. Annu Rev Med. 2007;58:221–237. [PubMed] [Google Scholar]

166. FitzGerald DJ, Wayne AS, Kreitman RJ, Pastan I. Treatment of hematologic malignancies with immunotoxins and antibody-drug conjugates. Cancer Res. 2011;71:6300–6309. [PMC free article] [PubMed] [Google Scholar]

167. Lawrence MS, Phillips KJ, Liu DR. Supercharging proteins can impart unusual resilience. J Am Chem Soc. 2007;129:10110–10112. [PMC free article] [PubMed] [Google Scholar]

168. Cronican JJ, Thompson DB, Beier KT, et al. Potent delivery of functional proteins into mammalian cells in vitro and in vivo using a supercharged protein. ACS Chem Biol. 2010;5:747–752. [PMC free article] [PubMed] [Google Scholar]

169. Cronican JJ, Beier KT, Davis TN, et al. A class of human proteins that deliver functional proteins into mammalian cells in vitro and in vivo. Chem Biol. 2011;18:833–838. [PMC free article] [PubMed] [Google Scholar]

170. Weisbart RH, Noritake DT, Wong AL, et al. A conserved anti-DNA antibody idiotype associated with nephritis in murine and human systemic lupus erythematosus. J Immunol. 1990;144:2653–2658. [PubMed] [Google Scholar]

171. Hansen JE, Chan G, Liu Y, et al. Targeting cancer with a lupus autoantibody. Sci Transl Med. 2012;4 157ra142. [PMC free article] [PubMed] [Google Scholar]

172. Lawlor MW, Armstrong D, Viola MG, et al. Enzyme replacement therapy rescues weakness and improves muscle pathology in mice with X-linked myotubular myopathy. Hum Mol Genet. 2013;22:1525–1538. [PMC free article] [PubMed] [Google Scholar]

173. Kaczmarczyk SJ, Sitaraman K, Young HA, et al. Protein delivery using engineered virus-like particles. Proc Natl Acad Sci. 2011;108:16998–17003. [PMC free article] [PubMed] [Google Scholar]

174. Tao P, Mahalingam M, Marasa BS, et al. In vitro and in vivo delivery of genes and proteins using the bacteriophage T4 DNA packaging machine. Proc Natl Acad Sci. 2013;110:5846–5851. [PMC free article] [PubMed] [Google Scholar]

175. Mallery DL, McEwan WA, Bidgood SR, et al. Antibodies mediate intracellular immunity through tripartite motif-containing 21 (TRIM21) Proc Natl Acad Sci. 2010;107:19985–19990. [PMC free article] [PubMed] [Google Scholar]

176. Torchilin V. Intracellular delivery of protein and peptide therapeutics. Drug Discov Today Technol. 2008;5:e95–e103. [PubMed] [Google Scholar]

177. Zelphati O, Wang Y, Kitada S, et al. Intracellular delivery of proteins with a new lipid-mediated delivery system. J Biol Chem. 2001;276:35103–35110. [PubMed] [Google Scholar]

178. Benjaminsen RV, Mattebjerg MA, Henriksen JR, et al. The possible “proton sponge” effect of polyethylenimine (PEI) does not include change in lysosomal pH. Mol Ther. 2013;21:149–157. [PMC free article] [PubMed] [Google Scholar]

179. Behr J-P. The proton sponge: a trick to enter cells the viruses did not exploit. Chim Int J Chem. 1997;51:34–36. [Google Scholar]

180. Lynn DM, Langer R. Degradable poly(β-amino esters): synthesis, characterization, and self-assembly with plasmid DNA. J Am Chem Soc. 2000;122:10761–10768. [Google Scholar]

181. Su X, Yang N, Wittrup KD, Irvine DJ. Synergistic antitumor activity from two-stage delivery of targeted toxins and endosome-disrupting nanoparticles. Biomacromolecules. 2013;14:1093–1102. [PMC free article] [PubMed] [Google Scholar]

182. Gu Z, Yan M, Hu B, et al. Protein nanocapsule weaved with enzymatically degradable polymeric network. Nano Lett. 2009;9:4533–4538. [PubMed] [Google Scholar]

183. Yan M, Du J, Gu Z, et al. A novel intracellular protein delivery platform based on single-protein nanocapsules. Nat Nanotechnol. 2010;5:48–53. [PubMed] [Google Scholar]

184. Biswas A, Joo K-I, Liu J, et al. Endoprotease-mediated intracellular protein delivery using nanocapsules. ACS Nano. 2011;5:1385–1394. [PubMed] [Google Scholar]

185. Malmsten M. Inorganic nanomaterials as delivery systems for proteins, peptides, DNA, and siRNA. Curr Opin Colloid Interface Sci. 2013;18:468–480. [Google Scholar]

186. Loosli H-R, Kessler H, Oschkinat H, et al. Peptide conformations. Part 31. The conformation of cyclosporin a in the crystal and in solution. Helv Chim Acta. 1985;68:682–704. [Google Scholar]

187. Bayer P, Kraft M, Ejchart A, et al. Structural studies of HIV-1 tat protein. J Mol Biol. 1995;247:529–535. [PubMed] [Google Scholar]

188. Feld GK, Thoren KL, Kintzer AF, et al. Structural basis for the unfolding of anthrax lethal factor by protective antigen oligomers. Nat Struct Mol Biol. 2010;17:1383–1390. [PMC free article] [PubMed] [Google Scholar]

189. Varghese Gupta S, Gupta D, Sun J, et al. Enhancing the intestinal membrane permeability of zanamivir: a carrier mediated prodrug approach. Mol Pharm. 2011;8:2358–2367. [PMC free article] [PubMed] [Google Scholar]


Page 2

Permeability coefficients of select molecules

SpeciesMoleculePermeabilitycoefficient

(cm/s)

Membrane typeReference
IonsNa+
K+
5.0 × 10−14
4.7 × 10−14
Artificial membranePapahadjopoulos et al. [40]
Small
molecules
O 22.3 × 101Artificial membraneSubczynski et al. [36]
CO 23.5 × 10−1Artificial membraneGutknecht et al. [37]
H 2 O3.4 × 10−3Artificial membraneWalter and Gutknecht [38]
EtOH2.1 × 10−3Erythrocyte
membrane
Stein and Lieb [1]
Steroids10−3 to 10−4Cell monolayerGiorgi and Stein [42]
Urea4.0 × 10−6Artificial membraneFinkelstein [35]
Glycerol5.4 × 10−6Artificial membraneOrbach and Finkelstein [39]
Small molecule
drugs
10−5 to 10−6Artificial membraneDobson et al. [112]
PeptidesCyclosporin A2.5 × 10−7Artificial membraneRezai et al. [45]
TAT2.7 × 10−9Artificial membraneJones and Howl [81]