Hydrocarbon Stapled Peptides as Modulators of Biological Function

ACS Chemical Biology

Volumn 10, Issue 6, 2015, Pages 1362-1375

  Cromm, Philipp M ^a,b   Spiegel, Jochen ^a,b   Grossmann, Tom N ^a,b,c  

^a MAX PLANCK INSTITUTE OF MOLECULAR PHYSIOLOGY   (Germany)

^b TU DORTMUND UNIVERSITY   (Germany)

^c CHEMICAL GENOMICS CENTRE OF THE MAX PLANCK SOCIETY   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ALRN 5281; ALRN 6924; ANTINEOPLASTIC AGENT; APOLIPOPROTEIN A1; ATSP 7041; BETA CATENIN; ENFUVIRTIDE; ESTROGEN RECEPTOR; GAG PROTEIN; GROWTH HORMONE RELEASING FACTOR; GUANOSINE TRIPHOSPHATASE; HYDROCARBON; INITIATION FACTOR 4E; INSULIN RECEPTOR; INSULIN RECEPTOR SUBSTRATE 1; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; NOTCH RECEPTOR; PEPTIDE; POLYPEPTIDE ANTIBIOTIC AGENT; PROTEIN MCL 1; PROTEIN MDM2; PROTEIN MDMX; PROTEIN P21; PROTEIN P53; TRANSCRIPTION FACTOR EZH2; UNCLASSIFIED DRUG; VASCULOTROPIN; ANTIMALARIAL AGENT; ANTIVIRUS AGENT; CELL SURFACE RECEPTOR;

ALPHA HELIX; AMINO ACID SEQUENCE; ANTIVIRAL ACTIVITY; CELL MEMBRANE; CELL SURVIVAL; CRYSTAL STRUCTURE; DRUG BIOAVAILABILITY; DRUG DELIVERY SYSTEM; DRUG HALF LIFE; HEMOLYSIS; HEPATITIS C; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; HYDROGEN BOND; MALARIA; MOLECULAR DYNAMICS; NONHUMAN; PEPTIDE SYNTHESIS; PLASMA HALF LIFE; POINT MUTATION; PRIORITY JOURNAL; PROTEIN CONFORMATION; PROTEIN CROSS LINKING; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; PROTEIN STRUCTURE; RESPIRATORY SYNCYTIAL VIRUS INFECTION; REVIEW; SIGNAL TRANSDUCTION; VIRUS INFECTIVITY; VIRUS NUCLEOCAPSID; VIRUS REPLICATION; WNT SIGNALING PATHWAY; AGONISTS; ANTAGONISTS AND INHIBITORS; CHEMICAL STRUCTURE; CHEMISTRY; DRUG DEVELOPMENT; GENE EXPRESSION REGULATION; GENETICS; HIV INFECTIONS; MALARIA, FALCIPARUM; METABOLISM; NEOPLASMS; PARASITOLOGY; PATHOLOGY; PROTEIN SECONDARY STRUCTURE; PROTEIN TERTIARY STRUCTURE; SYNTHESIS; VIROLOGY;

ANTIMALARIALS; ANTINEOPLASTIC AGENTS; ANTIVIRAL AGENTS; DRUG DISCOVERY; GENE EXPRESSION REGULATION; HEPATITIS C; HIV INFECTIONS; HUMANS; MALARIA, FALCIPARUM; MODELS, MOLECULAR; NEOPLASMS; PEPTIDES; PROTEIN STRUCTURE, SECONDARY; PROTEIN STRUCTURE, TERTIARY; RECEPTORS, CELL SURFACE; SIGNAL TRANSDUCTION;

EID: 84934996624     PISSN: 15548929     EISSN: 15548937     Source Type: Journal    
DOI: 10.1021/cb501020r     Document Type: Review

References (162)

1. Newman, D. J. and Cragg, G. M. (2012) Natural products as sources of new drugs over the 30 years from 1981 to 2010 J. Nat. Prod. 75, 311-335
2. Craik, D. J., Fairlie, D. P., Liras, S., and Price, D. (2013) The future of peptide-based drugs Chem. Biol. Drug. Des. 81, 136-147
3. Verdine, G. L. and Hilinski, G. J. (2012) All-hydrocarbon stapled peptides as Synthetic Cell-Accessible Mini-Proteins Drug Discovery Today: Technol. 9, e41-e47
4. Verdine, G. L. and Walensky, L. D. (2007) The Challenge of Drugging Undruggable Targets in Cancer: Lessons Learned from Targeting BCL-2 Family Members Clin. Cancer. Res. 13, 7264-7270
5. Milroy, L.-G., Grossmann, T. N., Hennig, S., Brunsveld, L., and Ottmann, C. (2014) Modulators of Protein-Protein Interactions Chem. Rev. 114, 4695-4748
6. Spiegel, J., Cromm, P. M., Zimmermann, G., Grossmann, T. N., and Waldmann, H. (2014) Small-molecule modulation of Ras signaling Nat. Chem. Biol. 10, 613-622
7. Kaspar, A. A. and Reichert, J. M. (2013) Future directions for peptide therapeutics development Drug Discovery Today 18, 807-817
8. Bock, J. E., Gavenonis, J., and Kritzer, J. A. (2013) Getting in Shape: Controlling Peptide Bioactivity and Bioavailability Using Conformational Constraints ACS Chem. Biol. 8, 488-499
9. Garcia, A. and Camarero, J. (2010) Biological Activities of Natural and Engineered Cyclotides, a Novel Molecular Scaffold for Peptide-Based Therapeutics Curr. Mol. Pharmacol. 3, 153-163
10. Poth, A. G., Chan, L. Y., and Craik, D. J. (2013) Cyclotides as grafting frameworks for protein engineering and drug design applications Biopolymers 100, 480-491
11. Hill, T. A., Shepherd, N. E., Diness, F., and Fairlie, D. P. (2014) Constraining cyclic peptides to mimic protein structure motifs Angew. Chem., Int. Ed. Engl. 53, 13020-13041
12. Pelay-Gimeno, M., Glas, A., Koch, O., and Grossmann, T. N. (2015) Structure-based design of inhibitors of protein-protein interactions: Mimicking peptide-binding epitopes Angew. Chem., Int. Ed. 10.1002/anie.201412070R1
13. Klein, M. A. (2014) Stabilized helical peptides: a strategy to target protein-protein interactions ACS Med. Chem. Lett. 5, 838-839
14. Milroy, L.-G. and Brunsveld, L. (2013) Pharmaceutical implications of helix length control in helix-mediated protein-protein interactions Future Med. Chem. 5, 2175-2183
15. Jochim, A. L. and Arora, P. S. (2009) Assessment of helical interfaces in protein-protein interactions Mol. Biosyst 5, 924-926
16. Guarracino, D. A., Bullock, B. N., and Arora, P. S. (2011) Protein-protein interactions in transcription: A fertile ground for helix mimetics Biopolymers 95, 1-7
17. Mahon, A. B. and Arora, P. S. (2012) End-Capped α-Helices as Modulators of Protein Function Drug Discovery Today: Technol. 9, e57-e62
18. Henchey, L. K., Jochim, A. L., and Arora, P. S. (2008) Contemporary strategies for the stabilization of peptides in the α-helical conformation Curr. Opin. Chem. Biol. 12, 692-697
19. Azzarito, V., Long, K., Murphy, N. S., and Wilson, A. J. (2013) Inhibition of α-helix-mediated protein-protein interactions using designed molecules Nat. Chem. 5, 161-173
20. Toniolo, C., Crisma, M., Formaggio, F., Valle, G., Cavicchioni, G., Precigoux, G., Aubry, A., and Kamphuis, J. (1993) Structures of peptides from alpha-amino acids methylated at the alpha-carbon Biopolymers 33, 1061-1072
21. Doig, A. J. and Baldwin, R. L. (1995) N- and C-capping preferences for all 20 amino acids in alpha-helical peptides Protein Sci. 4, 1325-1336
22. Doig, A. J. (2002) Recent advances in helix-coil theory Biophys. Chem. 101-102, 281-293
23. Bracken, C., Gulyas, J., Taylor, J. W., and Baum, J. (1994) Synthesis and Nuclear Magnetic Resonance Structure Determination of an.alpha.-Helical, Bicyclic, Lactam-Bridged Hexapeptide J. Am. Chem. Soc. 116, 6431-6432
24. Jackson, D. Y., King, D. S., Chmielewski, J., Singh, S., and Schultz, P. G. (1991) General approach to the synthesis of short.alpha.-helical peptides J. Am. Chem. Soc. 113, 9391-9392
25. Blackwell, H. E. and Grubbs, R. H. (1998) Highly Efficient Synthesis of Covalently Cross-Linked Peptide Helices by Ring-Closing Metathesis Angew. Chem., Int. Ed. Engl. 37, 3281-3284
26. Schafmeister, C. E., Po, J., and Verdine, G. L. (2000) An All-Hydrocarbon Cross-Linking System for Enhancing the Helicity and Metabolic Stability of Peptides J. Am. Chem. Soc. 122, 5891-5892
27. Kim, Y.-W., Kutchukian, P. S., and Verdine, G. L. (2010) Introduction of All-Hydrocarbon i, i +3 Staples into α-Helices via Ring-Closing Olefin Metathesis Org. Lett. 12, 3046-3049
28. Walensky, L. D., Kung, A. L., Escher, I., Malia, T. J., Barbuto, S., Wright, R. D., Wagner, G., Verdine, G. L., and Korsmeyer, S. J. (2004) Activation of Apoptosis in Vivo by a Hydrocarbon-Stapled BH3 Helix Science 305, 1466-1470
29. Guerlavais, V. and Sawyer, T. K. (2014) Advancements in Stapled Peptide Drug Discovery & Development, pp 331-345, Elsevier.
30. Sawyer, T. K., Guerlavais, V., Darlak, K., and Feyfant, E. (2015) CHAPTER 9. Macrocyclic α-Helical Peptide Drug Discovery. In Macrocycles in Drug Discovery, pp 339-366.
31. Wang, D., Chen, K., Kulp, J. L., III, and Arora, P. S. (2006) Evaluation of biologically relevant short alpha-helices stabilized by a main-chain hydrogen-bond surrogate J. Am. Chem. Soc. 128, 9248-9256
32. Boersma, M. D., Haase, H. S., Peterson-Kaufman, K. J., Lee, E. F., Clarke, O. B., Colman, P. M., Smith, B. J., Horne, W. S., Fairlie, W. D., and Gellman, S. H. (2012) Evaluation of diverse α/β-backbone patterns for functional α-helix mimicry: analogues of the Bim BH3 domain J. Am. Chem. Soc. 134, 315-323
33. Arkin, M. R., Tang, Y., and Wells, J. A. (2014) Small-Molecule Inhibitors of Protein-Protein Interactions: Progressing toward the Reality Chem. Biol. 21, 1102-1114
34. Shim, S. Y., Kim, Y.-W., and Verdine, G. L. (2013) A new i, i + 3 peptide stapling system for α-helix stabilization Chem. Biol. Drug. Des. 82, 635-642
35. Kutchukian, P. S., Yang, J. S., Verdine, G. L., and Shakhnovich, E. I. (2009) All-atom model for stabilization of alpha-helical structure in peptides by hydrocarbon staples J. Am. Chem. Soc. 131, 4622-4627
36. Hilinski, G. J., Kim, Y.-W., Hong, J., Kutchukian, P. S., Crenshaw, C. M., Berkovitch, S. S., Chang, A., Ham, S., and Verdine, G. L. (2014) Stitched α-Helical Peptides via Bis Ring-Closing Metathesis J. Am. Chem. Soc. 136, pp12314-12322
37. Kim, Y.-W., Grossmann, T. N., and Verdine, G. L. (2011) Synthesis of all-hydrocarbon stapled α-helical peptides by ring-closing olefin metathesis Nat. Protoc. 6, 761-771
38. Kim, Y.-W. and Verdine, G. L. (2009) Stereochemical effects of all-hydrocarbon tethers in i,i+4 stapled peptides Bioorg. Med. Chem. Lett. 19, 2533-2536
39. Bird, G. H., Madani, N., Perry, A. F., Princiotto, A. M., Supko, J. G., He, X., Gavathiotis, E., Sodroski, J. G., and Walensky, L. D. (2010) Hydrocarbon double-stapling remedies the proteolytic instability of a lengthy peptide therapeutic Proc. Natl. Acad. Sci. U.S.A. 107, 14093-14098
40. Chu, Q., Moellering, R. E., Hilinski, G. J., Kim, Y.-W., Grossmann, T. N., Yeh, J. T.-H., and Verdine, G. L. (2015) Towards understanding cell penetration by stapled peptides Med. Chem. Commun. 6, 111-119
41. Okamoto, T., Zobel, K., Fedorova, A., Quan, C., Yang, H., Fairbrother, W. J., Huang, D. C. S., Smith, B. J., Deshayes, K., and Czabotar, P. E. (2013) Stabilizing the pro-apoptotic BimBH3 helix (BimSAHB) does not necessarily enhance affinity or biological activity ACS Chem. Biol. 8, 297-302
42. Sun, T.-L., Sun, Y., Lee, C.-C., and Huang, H. W. (2013) Membrane permeability of hydrocarbon-cross-linked peptides Biophys. J. 104, 1923-1932
43. Li, Y.-C., Rodewald, L. W., Hoppmann, C., Wong, E. T., Lebreton, S., Safar, P., Patek, M., Wang, L., Wertman, K. F., and Wahl, G. M. (2014) A Versatile Platform to Analyze Low-Affinity and Transient Protein-Protein Interactions in Living Cells in Real Time Cell Rep. 9, 1946-1958
44. Bechara, C. and Sagan, S. (2013) Cell-penetrating peptides: 20 years later, where do we stand? FEBS Lett. 587, 1693-1702
45. Bird, G. H., Gavathiotis, E., LaBelle, J. L., Katz, S. G., and Walensky, L. D. (2014) Distinct BimBH3 (BimSAHB) Stapled Peptides for Structural and Cellular Studies ACS Chem. Biol. 9, 831-837
46. Walensky, L. D. and Bird, G. H. (2014) Hydrocarbon-Stapled Peptides: Principles, Practice, and Progress J. Med. Chem. 57, 6275-6288
47. Huseby, D., Barklis, R. L., Alfadhli, A., and Barklis, E. (2005) Assembly of human immunodeficiency virus precursor gag proteins J. Biol. Chem. 280, 17664-17670
48. Göttlinger, H. G. (2001) The HIV-1 assembly machine AIDS 15, S13-S20
49. Taiwo, B., Murphy, R. L., and Katlama, C. (2010) Novel antiretroviral combinations in treatment-experienced patients with HIV infection: rationale and results Drugs 70, 1629-1642
50. Zhang, H., Curreli, F., Zhang, X., Bhattacharya, S., Waheed, A. A., Cooper, A., Cowburn, D., Freed, E. O., and Debnath, A. K. (2011) Antiviral activity of α-helical stapled peptides designed from the HIV-1 capsid dimerization domain Retrovirology 8, 28
51. Zhang, H., Curreli, F., Waheed, A. A., Mercredi, P. Y., Mehta, M., Bhargava, P., Scacalossi, D., Tong, X., Lee, S., Cooper, A., Summers, M. F., Freed, E. O., and Debnath, A. K. (2013) Dual-acting stapled peptides target both HIV-1 entry and assembly Retrovirology 10, 136
52. Zhang, H., Zhao, Q., Bhattacharya, S., Waheed, A. A., Tong, X., Hong, A., Heck, S., Curreli, F., Goger, M., Cowburn, D., Freed, E. O., and Debnath, A. K. (2008) A Cell-penetrating Helical Peptide as a Potential HIV-1 Inhibitor J. Mol. Biol. 378, 565-580
53. Bhattacharya, S., Zhang, H., Cowburn, D., and Debnath, A. K. (2012) Novel structures of self-associating stapled peptides Biopolymers 97, 253-264
54. Sticht, J., Humbert, M., Findlow, S., Bodem, J., Müller, B., Dietrich, U., Werner, J., and Kräusslich, H.-G. (2005) A peptide inhibitor of HIV-1 assembly in vitro Nat. Struct. Mol. Biol. 12, 671-677
55. Ternois, F., Sticht, J., Duquerroy, S., Kräusslich, H.-G., and Rey, F. A. (2005) The HIV-1 capsid protein C-terminal domain in complex with a virus assembly inhibitor Nat. Struct. Mol. Biol. 12, 678-682
56. Bhattacharya, S., Zhang, H., Debnath, A. K., and Cowburn, D. (2008) Solution Structure of a Hydrocarbon Stapled Peptide Inhibitor in Complex with Monomeric C-terminal Domain of HIV-1 Capsid J. Biol. Chem. 283, 16274-16278
57. Kilby, J. M., Hopkins, S., Venetta, T. M., DiMassimo, B., Cloud, G. A., Lee, J. Y., Alldredge, L., Hunter, E., Lambert, D., Bolognesi, D., Matthews, T., Johnson, M. R., Nowak, M. A., Shaw, G. M., and Saag, M. S. (1998) Potent suppression of HIV-1 replication in humans by T-20, a peptide inhibitor of gp41-mediated virus entry Nat. Med. 4, 1302-1307
58. Kilby, J. M., Lalezari, J. P., Eron, J. J., Carlson, M., Cohen, C., Arduino, R. C., Goodgame, J. C., Gallant, J. E., Volberding, P., Murphy, R. L., Valentine, F., Saag, M. S., Nelson, E. L., Sista, P. R., and Dusek, A. (2002) The safety, plasma pharmacokinetics, and antiviral activity of subcutaneous enfuvirtide (T-20), a peptide inhibitor of gp41-mediated virus fusion, in HIV-infected adults AIDS Res. Hum. Retroviruses 18, 685-693
59. Wei, X., Decker, J. M., Liu, H., Zhang, Z., Arani, R. B., Kilby, J. M., Saag, M. S., Wu, X., Shaw, G. M., and Kappes, J. C. (2002) Emergence of Resistant Human Immunodeficiency Virus Type 1 in Patients Receiving Fusion Inhibitor (T-20) Monotherapy Antimicrob. Agents Chemother. 46, 1896-1905
60. Bird, G. H., Irimia, A., Ofek, G., Kwong, P. D., Wilson, I. A., and Walensky, L. D. (2014) Stapled HIV-1 peptides recapitulate antigenic structures and engage broadly neutralizing antibodies Nat. Struct. Mol. Biol. 21, 1058-1067
61. Li, H.-Y., Zawahir, Z., Song, L.-D., Long, Y.-Q., and Neamati, N. (2006) Sequence-based design and discovery of peptide inhibitors of HIV-1 integrase: insight into the binding mode of the enzyme J. Med. Chem. 49, 4477-4486
62. Suzuki, S., Urano, E., Hashimoto, C., Tsutsumi, H., Nakahara, T., Tanaka, T., Nakanishi, Y., Maddali, K., Han, Y., Hamatake, M., Miyauchi, K., Pommier, Y., Beutler, J. A., Sugiura, W., Fuji, H., Hoshino, T., Itotani, K., Nomura, W., Narumi, T., Yamamoto, N., Komano, J. A., and Tamamura, H. (2010) Peptide HIV-1 integrase inhibitors from HIV-1 gene products J. Med. Chem. 53, 5356-5360
63. Zawahir, Z. and Neamati, N. (2006) Inhibition of HIV-1 integrase activity by synthetic peptides derived from the HIV-1 HXB2 Pol region of the viral genome Bioorg. Med. Chem. Lett. 16, 5199-5202
64. Long, Y.-Q., Huang, S.-X., Zawahir, Z., Xu, Z.-L., Li, H., Sanchez, T. W., Zhi, Y., Houwer, S., de Christ, F., Debyser, Z., and Neamati, N. (2013) Design of cell-permeable stapled peptides as HIV-1 integrase inhibitors J. Med. Chem. 56, 5601-5612
65. Nomura, W., Aikawa, H., Ohashi, N., Urano, E., Métifiot, M., Fujino, M., Maddali, K., Ozaki, T., Nozue, A., Narumi, T., Hashimoto, C., Tanaka, T., Pommier, Y., Yamamoto, N., Komano, J. A., Murakami, T., and Tamamura, H. (2013) Cell-permeable stapled peptides based on HIV-1 integrase inhibitors derived from HIV-1 gene products ACS Chem. Biol. 8, 2235-2244
66. Bird, G. H., Boyapalle, S., Wong, T., Opoku-Nsiah, K., Bedi, R., Crannell, W. C., Perry, A. F., Nguyen, H., Sampayo, V., Devareddy, A., Mohapatra, S., Mohapatra, S. S., and Walensky, L. D. (2014) Mucosal delivery of a double-stapled RSV peptide prevents nasopulmonary infection J. Clin. Invest. 124, 2113-2124
67. Cui, H.-K., Qing, J., Guo, Y., Wang, Y.-J., Cui, L.-J., He, T.-H., Zhang, L., and Liu, L. (2013) Stapled peptide-based membrane fusion inhibitors of hepatitis C virus Bioorg. Med. Chem. 21, 3547-3554
68. Lambert, D. M., Barney, S., Lambert, A. L., Guthrie, K., Medinas, R., Davis, D. E., Bucy, T., Erickson, J., Merutka, G., and Petteway, S. R. (1996) Peptides from conserved regions of paramyxovirus fusion (F) proteins are potent inhibitors of viral fusion Proc. Natl. Acad. Sci. U.S.A. 93, 2186-2191
69. Pham, T. K., Kim, D.-H., Lee, B.-J., and Kim, Y.-W. (2013) Truncated and constrained helical analogs of antimicrobial esculentin-2EM Bioorg. Med. Chem. Lett. 23, 6717-6720
70. Chapuis, H., Slaninová, J., Bednárová, L., Monincová, L., Buděšínský, M., and Čeřovský, V. (2012) Effect of hydrocarbon stapling on the properties of α-helical antimicrobial peptides isolated from the venom of hymenoptera Amino Acids 43, 2047-2058
71. Bellmann-Sickert, K., Stone, T. A., Poulsen, B. E., and Deber, C. M. (2014) Efflux by Small Multidrug Resistance Proteins is Inhibited by Membrane-Interactive Helix-Stapled Peptides J. Biol. Chem. 290, 1752-1759
72. Zasloff, M. (2002) Antimicrobial peptides of multicellular organisms Nature 415, 389-395
73. Kourtesi, C., Ball, A. R., Huang, Y.-Y., Jachak, S. M., Vera, D., Mariano, A., Khondkar, P., Gibbons, S., Hamblin, M. R., and Tegos, G. P. (2013) Microbial efflux systems and inhibitors: approaches to drug discovery and the challenge of clinical implementation Open Microbiol. J. 7, 34-52
74. Poulsen, B. E., Rath, A., and Deber, C. M. (2009) The assembly motif of a bacterial small multidrug resistance protein J. Biol. Chem. 284, 9870-9875
75. Bosch, J., Turley, S., Roach, C. M., Daly, T. M., Bergman, L. W., and Hol, W. G. J. (2007) The closed MTIP-myosin A-tail complex from the malaria parasite invasion machinery J. Mol. Biol. 372, 77-88
76. Bergman, L. W. (2002) Myosin A tail domain interacting protein (MTIP) localizes to the inner membrane complex of Plasmodium sporozoites J. Cell Sci. 116, 39-49
77. Baum, J., Papenfuss, A. T., Baum, B., Speed, T. P., and Cowman, A. F. (2006) Regulation of apicomplexan actin-based motility Nat. Rev. Microbiol. 4, 621-628
78. Douse, C. H., Maas, S. J., Thomas, J. C., Garnett, J. A., Sun, Y., Cota, E., and Tate, E. W. (2014) Crystal structures of stapled and hydrogen bond surrogate peptides targeting a fully buried protein-helix interaction ACS Chem. Biol. 9, 2204-2209
79. Vousden, K. H. and Lane, D. P. (2007) p53 in health and disease Nat. Rev. Mol. Cell Biol. 8, 275-283
80. Hock, A. and Vousden, K. H. (2010) Regulation of the p53 pathway by ubiquitin and related proteins Int. J. Biochem. Cell Biol. 42, 1618-1621
81. Huang, L., Yan, Z., Liao, X., Li, Y., Yang, J., Wang, Z.-G., Zuo, Y., Kawai, H., Shadfan, M., Ganapathy, S., and Yuan, Z.-M. (2011) The p53 inhibitors MDM2/MDMX complex is required for control of p53 activity in vivo Proc. Natl. Acad. Sci. U.S.A. 108, 12001-12006
82. Kussie, P. H., Gorina, S., Marechal, V., Elenbaas, B., Moreau, J., Levine, A. J., and Pavletich, N. P. (1996) Structure of the MDM2 Oncoprotein Bound to the p53 Tumor Suppressor Transactivation Domain Science 274, 948-953
83. Vassilev, L. T., Vu, B. T., Graves, B., Carvajal, D., Podlaski, F., Filipovic, Z., Kong, N., Kammlott, U., Lukacs, C., Klein, C., Fotouhi, N., and Liu, E. A. (2004) In vivo activation of the p53 pathway by small-molecule antagonists of MDM2 Science 303, 844-848
84. Vu, B., Wovkulich, P., Pizzolato, G., Lovey, A., Ding, Q., Jiang, N., Liu, J.-J., Zhao, C., Glenn, K., Wen, Y., Tovar, C., Packman, K., Vassilev, L., and Graves, B. (2013) Discovery of RG7112: A Small-Molecule MDM2 Inhibitor in Clinical Development ACS Med. Chem. Lett. 4, 466-469
85. Khoo, K. H., Hoe, K. K., Verma, C. S., and Lane, D. P. (2014) Drugging the p53 pathway: understanding the route to clinical efficacy Nat. Rev. Drug Discovery 13, 217-236
86. Brown, C. J., Lain, S., Verma, C. S., Fersht, A. R., and Lane, D. P. (2009) Awakening guardian angels: drugging the p53 pathway Nat. Rev. Cancer 9, 862-873
87. Bernal, F., Tyler, A. F., Korsmeyer, S. J., Walensky, L. D., and Verdine, G. L. (2007) Reactivation of the p53 Tumor Suppressor Pathway by a Stapled p53 Peptide J. Am. Chem. Soc. 129, 2456-2457
88. Bernal, F., Wade, M., Godes, M., Davis, T. N., Whitehead, D. G., Kung, A. L., Wahl, G. M., and Walensky, L. D. (2010) A Stapled p53 Helix Overcomes HDMX-Mediated Suppression of p53 Cancer Cell 18, 411-422
89. Gembarska, A., Luciani, F., Fedele, C., Russell, E. A., Dewaele, M., Villar, S., Zwolinska, A., Haupt, S., Lange, J., de Yip, D., Goydos, J., Haigh, J. J., Haupt, Y., Larue, L., Jochemsen, A., Shi, H., Moriceau, G., Lo, R. S., Ghanem, G., Shackleton, M., Bernal, F., and Marine, J.-C. (2012) MDM4 is a key therapeutic target in cutaneous melanoma Nat. Med. 18, 1239-1247
90. Guo, Z., Mohanty, U., Noehre, J., Sawyer, T. K., Sherman, W., and Krilov, G. (2010) Probing the alpha-helical structural stability of stapled p53 peptides: molecular dynamics simulations and analysis Chem. Biol. Drug. Des. 75, 348-359
91. Guo, Z., Streu, K., Krilov, G., and Mohanty, U. (2014) Probing the origin of structural stability of single and double stapled p53 peptide analogs bound to MDM2 Chem. Biol. Drug. Des. 83, 631-642
92. Sim, A. Y. L., Joseph, T., Lane, D. P., and Verma, C. (2014) Mechanism of Stapled Peptide Binding to MDM2: Possible Consequences for Peptide Design J. Chem. Theory Comput. 10, 1753-1761
93. Baek, S., Kutchukian, P. S., Verdine, G. L., Huber, R., Holak, T. A., Lee, K. W., and Popowicz, G. M. (2012) Structure of the stapled p53 peptide bound to Mdm2 J. Am. Chem. Soc. 134, 103-106
94. Pazgier, M., Liu, M., Zou, G., Yuan, W., Li, C., Li, C., Li, J., Monbo, J., Zella, D., Tarasov, S. G., and Lu, W. (2009) Structural basis for high-affinity peptide inhibition of p53 interactions with MDM2 and MDMX Proc. Natl. Acad. Sci. U.S.A. 106, 4665-4670
95. Li, C., Pazgier, M., Li, C., Yuan, W., Liu, M., Wei, G., Lu, W.-Y., and Lu, W. (2010) Systematic mutational analysis of peptide inhibition of the p53-MDM2/MDMX interactions J. Mol. Biol. 398, 200-213
96. Brown, C. J., Quah, S. T., Jong, J., Goh, A. M., Chiam, P. C., Khoo, K. H., Choong, M. L., Lee, M. A., Yurlova, L., Zolghadr, K., Joseph, T. L., Verma, C. S., and Lane, D. P. (2013) Stapled peptides with improved potency and specificity that activate p53 ACS Chem. Biol. 8, 506-512
97. Wei, S. J., Joseph, T., Chee, S., Li, L., Yurlova, L., Zolghadr, K., Brown, C., Lane, D., Verma, C., and Ghadessy, F. (2013) Inhibition of nutlin-resistant HDM2 mutants by stapled peptides PLoS One 8, e81068
98. Chee, S. M. Q., Wongsantichon, J., Soo Tng, Q., Robinson, R., Joseph, T. L., Verma, C., Lane, D. P., Brown, C. J., and Ghadessy, F. J. (2014) Structure of a stapled Peptide antagonist bound to nutlin-resistant mdm2 PLoS One 9, e104914
99. Hu, B., Gilkes, D. M., and Chen, J. (2007) Efficient p53 activation and apoptosis by simultaneous disruption of binding to MDM2 and MDMX Cancer Res. 67, 8810-8817
100. Chang, Y. S., Graves, B., Guerlavais, V., Tovar, C., Packman, K., To, K.-H., Olson, K. A., Kesavan, K., Gangurde, P., Mukherjee, A., Baker, T., Darlak, K., Elkin, C., Filipovic, Z., Qureshi, F. Z., Cai, H., Berry, P., Feyfant, E., Shi, X. E., Horstick, J., Annis, D. A., Manning, A. M., Fotouhi, N., Nash, H., Vassilev, L. T., and Sawyer, T. K. (2013) Stapled α-helical peptide drug development: a potent dual inhibitor of MDM2 and MDMX for p53-dependent cancer therapy Proc. Natl. Acad. Sci. U.S.A. 110, E3445-54
101. Huber, K. L., Ghosh, S., and Hardy, J. A. (2012) Inhibition of caspase-9 by stabilized peptides targeting the dimerization interface Biopolymers 98, 451-465
102. Danial, N. N. (2007) BCL-2 family proteins: critical checkpoints of apoptotic cell death Clin. Cancer Res. 13, 7254-7263
103. Walensky, L. D., Pitter, K., Morash, J., Oh, K. J., Barbuto, S., Fisher, J., Smith, E., Verdine, G. L., and Korsmeyer, S. J. (2006) A Stapled BID BH3 Helix Directly Binds and Activates BAX Mol. Cell 24, 199-210
104. Hamacher, K., Hübsch, A., and McCammon, J. A. (2006) A minimal model for stabilization of biomolecules by hydrocarbon cross-linking J. Chem. Phys. 124, 164907
105. Danial, N. N., Walensky, L. D., Zhang, C.-Y., Choi, C. S., Fisher, J. K., Molina, A. J. A., Datta, S. R., Pitter, K. L., Bird, G. H., Wikstrom, J. D., Deeney, J. T., Robertson, K., Morash, J., Kulkarni, A., Neschen, S., Kim, S., Greenberg, M. E., Corkey, B. E., Shirihai, O. S., Shulman, G. I., Lowell, B. B., and Korsmeyer, S. J. (2008) Dual role of proapoptotic BAD in insulin secretion and beta cell survival Nat. Med. 14, 144-153
106. Braun, C. R., Mintseris, J., Gavathiotis, E., Bird, G. H., Gygi, S. P., and Walensky, L. D. (2010) Photoreactive Stapled BH3 Peptides to Dissect the BCL-2 Family Interactome Chem. Biol. 17, 1325-1333
107. Szlyk, B., Braun, C. R., Ljubicic, S., Patton, E., Bird, G. H., Osundiji, M. A., Matschinsky, F. M., Walensky, L. D., and Danial, N. N. (2014) A phospho-BAD BH3 helix activates glucokinase by a mechanism distinct from that of allosteric activators Nat. Struct. Mol. Biol. 21, 36-42
108. Gavathiotis, E., Suzuki, M., Davis, M. L., Pitter, K., Bird, G. H., Katz, S. G., Tu, H.-C., Kim, H., Cheng, E. H.-Y., Tjandra, N., and Walensky, L. D. (2008) BAX activation is initiated at a novel interaction site Nature 455, 1076-1081
109. Reynolds, C., Roderick, J. E., Labelle, J. L., Bird, G., Mathieu, R., Bodaar, K., Colon, D., Pyati, U., Stevenson, K. E., Qi, J., Harris, M., Silverman, L. B., Sallan, S. E., Bradner, J. E., Neuberg, D. S., Look, A. T., Walensky, L. D., Kelliher, M. A., and Gutierrez, A. (2014) Repression of BIM mediates survival signaling by MYC and AKT in high-risk T-cell acute lymphoblastic leukemia Leukemia 28, 1819-1827
110. Stewart, M. L., Fire, E., Keating, A. E., and Walensky, L. D. (2010) The MCL-1 BH3 helix is an exclusive MCL-1 inhibitor and apoptosis sensitizer Nat. Chem. Biol. 6, 595-601
111. Cohen, N. A., Stewart, M. L., Gavathiotis, E., Tepper, J. L., Bruekner, S. R., Koss, B., Opferman, J. T., and Walensky, L. D. (2012) A competitive stapled peptide screen identifies a selective small molecule that overcomes MCL-1-dependent leukemia cell survival Chem. Biol. 19, 1175-1186
112. Joseph, T. L., Lane, D. P., and Verma, C. S. (2012) Stapled BH3 peptides against MCL-1: mechanism and design using atomistic simulations PLoS One 7, e43985
113. Phillips, C., Roberts, L. R., Schade, M., Bazin, R., Bent, A., Davies, N. L., Moore, R., Pannifer, A. D., Pickford, A. R., Prior, S. H., Read, C. M., Scott, A., Brown, D. G., Xu, B., and Irving, S. L. (2011) Design and structure of stapled peptides binding to estrogen receptors J. Am. Chem. Soc. 133, 9696-9699
114. Sviridov, D. O., Ikpot, I. Z., Stonik, J., Drake, S. K., Amar, M., Osei-Hwedieh, D. O., Piszczek, G., Turner, S., and Remaley, A. T. (2011) Helix stabilization of amphipathic peptides by hydrocarbon stapling increases cholesterol efflux by the ABCA1 transporter Biochem. Biophys. Res. Commun. 410, 446-451
115. Green, B. R., Klein, B. D., Lee, H.-K., Smith, M. D., Steve White, H., and Bulaj, G. (2013) Cyclic analogs of galanin and neuropeptide Y by hydrocarbon stapling Bioorg. Med. Chem. 21, 303-310
116. Platt, R. J., Han, T. S., Green, B. R., Smith, M. D., Skalicky, J., Gruszczynski, P., White, H. S., Olivera, B., Bulaj, G., and Gajewiak, J. (2012) Stapling mimics noncovalent interactions of γ-carboxyglutamates in conantokins, peptidic antagonists of N-methyl-D-aspartic acid receptors J. Biol. Chem. 287, 20727-20736
117. Giordanetto, F., Revell, J. D., Knerr, L., Hostettler, M., Paunovic, A., Priest, C., Janefeldt, A., and Gill, A. (2013) Stapled Vasoactive Intestinal Peptide (VIP) Derivatives Improve VPAC2 Agonism and Glucose-Dependent Insulin Secretion ACS Med. Chem. Lett. 4, 1163-1168
118. Sinclair, J. K.-L., Denton, E. V., and Schepartz, A. (2014) Inhibiting Epidermal Growth Factor Receptor at a Distance J. Am. Chem. Soc. 136, 11232-11235
119. Sinclair, J. K.-L. and Schepartz, A. (2014) Influence of Macrocyclization on Allosteric, Juxtamembrane-Derived, Stapled Peptide Inhibitors of the Epidermal Growth Factor Receptor (EGFR) Org. Lett. 16, 4916-4919
120. Björnström, L. and Sjöberg, M. (2005) Mechanisms of estrogen receptor signaling: convergence of genomic and nongenomic actions on target genes Mol. Endocrinol. 19, 833-842
121. Heldring, N., Pike, A., Andersson, S., Matthews, J., Cheng, G., Hartman, J., Tujague, M., Ström, A., Treuter, E., Warner, M., and Gustafsson, J.-A. (2007) Estrogen receptors: how do they signal and what are their targets Physiol. Rev. 87, 905-931
122. Nettles, K. W., Bruning, J. B., Gil, G., Nowak, J., Sharma, S. K., Hahm, J. B., Kulp, K., Hochberg, R. B., Zhou, H., Katzenellenbogen, J. A., Katzenellenbogen, B. S., Kim, Y., Joachmiak, A., and Greene, G. L. (2008) NFkappaB selectivity of estrogen receptor ligands revealed by comparative crystallographic analyses Nat. Chem. Biol. 4, 241-247
123. McIntosh, J. M., Olivera, B. M., Cruz, L. J., and Gray, W. R. (1984) Gamma-carboxyglutamate in a neuroactive toxin J. Biol. Chem. 259, 14343-14346
124. Castellin, F. and Porok, M. (2000) Conantokins Inhibitors of Ion Flow through the N-Methyl-D-Aspartate Receptor Channels Curr. Drug. Targets. 1, 219-235
125. Cnudde, S. E., Prorok, M., Dai, Q., Castellino, F. J., and Geiger, J. H. (2007) The crystal structures of the calcium-bound con-G and con-T[K7gamma] dimeric peptides demonstrate a metal-dependent helix-forming motif J. Am. Chem. Soc. 129, 1586-1593
126. Panagotopulos, S. E., Witting, S. R., Horace, E. M., Hui, D. Y., Maiorano, J. N., and Davidson, W. S. (2002) The role of apolipoprotein A-I helix 10 in apolipoprotein-mediated cholesterol efflux via the ATP-binding cassette transporter ABCA1 J. Biol. Chem. 277, 39477-39484
127. Cantley, L. C. (2002) The phosphoinositide 3-kinase pathway Science 296, 1655-1657
128. Yarden, Y. and Pines, G. (2012) The ERBB network: at last, cancer therapy meets systems biology Nat. Rev. Cancer 12, 553-563
129. Cohen, S. (1962) Isolation of a mouse submaxillary gland protein accelerating incisor eruption and eyelid opening in the new-born animal J. Biol. Chem. 237, 1555-1562
130. Taylor, J. M., Mitchell, W. M., and Cohen, S. (1974) Characterization of the binding protein for epidermal growth factor J. Biol. Chem. 249, 2188-2194
131. Cohen, S., Carpenter, G., and King, L. (1980) Epidermal growth factor-receptor-protein kinase interactions. Co-purification of receptor and epidermal growth factor-enhanced phosphorylation activity J. Biol. Chem. 255, 4834-4842
132. Ciardiello, F. (2000) Epidermal growth factor receptor tyrosine kinase inhibitors as anticancer agents Drugs 60 (Suppl 1) 25-32 and discussion 41-42
133. Boran, A. D. W., Seco, J., Jayaraman, V., Jayaraman, G., Zhao, S., Reddy, S., Chen, Y., and Iyengar, R. (2012) A potential peptide therapeutic derived from the juxtamembrane domain of the epidermal growth factor receptor PLoS One 7, e49702
134. Thiel, K. W. and Carpenter, G. (2007) Epidermal growth factor receptor juxtamembrane region regulates allosteric tyrosine kinase activation Proc. Natl. Acad. Sci. U.S.A. 104, 19238-19243
135. Jura, N., Endres, N. F., Engel, K., Deindl, S., Das, R., Lamers, M. H., Wemmer, D. E., Zhang, X., and Kuriyan, J. (2009) Mechanism for activation of the EGF receptor catalytic domain by the juxtamembrane segment Cell 137, 1293-1307
136. Patgiri, A., Yadav, K. K., Arora, P. S., and Bar-Sagi, D. (2011) An orthosteric inhibitor of the Ras-Sos interaction Nat. Chem. Biol. 7, 585-587
137. Spiegel, J., Cromm, P. M., Itzen, A., Goody, R. S., Grossmann, T. N., and Waldmann, H. (2014) Direct targeting of Rab-GTPase-effector interactions Angew. Chem., Int. Ed. Engl. 53, 2498-2503
138. Hao, Y., Wang, C., Cao, B., Hirsch, B. M., Song, J., Markowitz, S. D., Ewing, R. M., Sedwick, D., Liu, L., Zheng, W., and Wang, Z. (2013) Gain of interaction with IRS1 by p110α-helical domain mutants is crucial for their oncogenic functions Cancer Cell 23, 583-593
139. Wang, Y., Ho, T. G., Bertinetti, D., Neddermann, M., Franz, E., Mo, G. C. H., Schendowich, L. P., Sukhu, A., Spelts, R. C., Zhang, J., Herberg, F. W., and Kennedy, E. J. (2014) Isoform-selective disruption of AKAP-localized PKA using hydrocarbon stapled peptides ACS Chem. Biol. 9, 635-642
140. Yang, Y., Schmitz, R., Mitala, J., Whiting, A., Xiao, W., Ceribelli, M., Wright, G. W., Zhao, H., Yang, Y., Xu, W., Rosenwald, A., Ott, G., Gascoyne, R. D., Connors, J. M., Rimsza, L. M., Campo, E., Jaffe, E. S., Delabie, J., Smeland, E. B., Braziel, R. M., Tubbs, R. R., Cook, J. R., Weisenburger, D. D., Chan, W. C., Wiestner, A., Kruhlak, M. J., Iwai, K., Bernal, F., and Staudt, L. M. (2014) Essential role of the linear ubiquitin chain assembly complex in lymphoma revealed by rare germline polymorphisms Cancer Discovery 4, 480-493
141. Moellering, R. E., Cornejo, M., Davis, T. N., Bianco, C. D., Aster, J. C., Blacklow, S. C., Kung, A. L., Gilliland, D. G., Verdine, G. L., and Bradner, J. E. (2009) Direct inhibition of the NOTCH transcription factor complex Nature 462, 182-188
142. Grossmann, T. N., Yeh, J. T.-H., Bowman, B. R., Chu, Q., Moellering, R. E., and Verdine, G. L. (2012) Inhibition of oncogenic Wnt signaling through direct targeting of β-catenin Proc. Natl. Acad. Sci. U.S.A. 109, 17942-17947
143. Takada, K., Zhu, Di, Bird, G. H., Sukhdeo, K., Zhao, J.-J., Mani, M., Lemieux, M., Carrasco, D. E., Ryan, J., Horst, D., Fulciniti, M., Munshi, N. C., Xu, W., Kung, A. L., Shivdasani, R. A., Walensky, L. D., and Carrasco, D. R. (2012) Targeted disruption of the BCL9/β-catenin complex inhibits oncogenic Wnt signaling Sci. Transl. Med. 4, 148ra117
144. Kim, W., Bird, G. H., Neff, T., Guo, G., Kerenyi, M. A., Walensky, L. D., and Orkin, S. H. (2013) Targeted disruption of the EZH2-EED complex inhibits EZH2-dependent cancer Nat. Chem. Biol. 9, 643-650
145. Bray, S. J. (2006) Notch signalling: a simple pathway becomes complex Nat. Rev. Mol. Cell Biol. 7, 678-689
146. Weng, A. P., Ferrando, A. A., Lee, W., Morris, J. P., Silverman, L. B., Sanchez-Irizarry, C., Blacklow, S. C., Look, A. T., and Aster, J. C. (2004) Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia Science 306, 269-271
147. Cui, H.-K., Zhao, B., Li, Y., Guo, Y., Hu, H., Liu, L., and Chen, Y.-G. (2013) Design of stapled α-helical peptides to specifically activate Wnt/β-catenin signaling Cell Res. 23, 581-584
148. Hahne, G. and Grossmann, T. N. (2013) Direct targeting of β-catenin: Inhibition of protein-protein interactions for the inactivation of Wnt signaling Bioorg. Med. Chem. 21, 4020-4026
149. Clevers, H. and Nusse, R. (2012) Wnt/β-catenin signaling and disease Cell 149, 1192-1205
150. Benedetti, A. de and Graff, J. R. (2004) eIF-4E expression and its role in malignancies and metastases Oncogene 23, 3189-3199
151. Culjkovic, B., Topisirovic, I., and Borden, K. L. (2007) Controlling Gene Expression through RNA Regulons: The Role of the Eukaryotic Translation Initiation Factor eIF4E Cell Cycle 6, 65-69
152. Zhou, W., Quah, S. T., Verma, C. S., Liu, Y., Lane, D. P., and Brown, C. J. (2012) Improved eIF4E binding peptides by phage display guided design: plasticity of interacting surfaces yield collective effects PLoS One 7, e47235
153. Lama, D., Quah, S. T., Verma, C. S., Lakshminarayanan, R., Beuerman, R. W., Lane, D. P., and Brown, C. J. (2013) Rational optimization of conformational effects induced by hydrocarbon staples in peptides and their binding interfaces Sci. Rep. 3, 3451
154. Frank, A. O., Vangamudi, B., Feldkamp, M. D., Souza-Fagundes, E. M., Luzwick, J. W., Cortez, D., Olejniczak, E. T., Waterson, A. G., Rossanese, O. W., Chazin, W. J., and Fesik, S. W. (2014) Discovery of a potent stapled helix peptide that binds to the 70N domain of replication protein A J. Med. Chem. 57, 2455-2461
155. Fanning, E., Klimovich, V., and Nager, A. R. (2006) A dynamic model for replication protein A (RPA) function in DNA processing pathways Nucleic Acids Res. 34, 4126-4137
156. Tan, J.-z., Yan, Y., Wang, X.-x., Jiang, Y., and Xu, H. E. (2014) EZH2: biology, disease, and structure-based drug discovery Acta Pharmacol. Sin. 35, 161-174
157. Brock, R. (2014) The uptake of arginine-rich cell-penetrating peptides: putting the puzzle together Bioconjugate Chem. 25, 863-868
158. Nakase, I., Takeuchi, T., Tanaka, G., and Futaki, S. (2008) Methodological and cellular aspects that govern the internalization mechanisms of arginine-rich cell-penetrating peptides Adv. Drug Delivery Rev. 60, 598-607
159. Shi, X. E., Wales, T. E., Elkin, C., Kawahata, N., Engen, J. R., and Annis, D. A. (2013) Hydrogen exchange-mass spectrometry measures stapled peptide conformational dynamics and predicts pharmacokinetic properties Anal. Chem. 85, 11185-11188
160. de Araujo, A. D., Hoang, H. N., Kok, W. M., Diness, F., Gupta, P., Hill, T. A., Driver, R. W., Price, D. A., Liras, S., and Fairlie, D. P. (2014) Comparative α-Helicity of Cyclic Pentapeptides in Water Angew. Chem., Int. Ed. 53, 6965-6969
161. Gavenonis, J., Jonas, N. E., and Kritzer, J. A. (2014) Potential C-terminal-domain inhibitors of heat shock protein 90 derived from a C-terminal peptide helix Bioorg. Med. Chem. 22, 3989-3993
162. Glas, A., Bier, D., Hahne, G., Rademacher, C., Ottmann, C., and Grossmann, T. N. (2014) Constrained Peptides with Target-Adapted Cross-Links as Inhibitors of a Pathogenic Protein-Protein Interaction Angew. Chem., Int. Ed. 53, 2489-2493