Hydrocarbon-stapled peptides: Principles, practice, and progress

Journal of Medicinal Chemistry

Volumn 57, Issue 15, 2014, Pages 6275-6288

  Walensky, Loren D ^a,b   Bird, Gregory H ^a  

^a DANA FARBER CANCER INSTITUTE   (United States)

^b BOSTON CHILDREN S HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

HYDROCARBON; PEPTIDES AND PROTEINS BY PEPTIDE STRUCTURE; STAPLED PEPTIDE; UNCLASSIFIED DRUG; ALANINE; BAX PROTEIN (53-86); CROSS LINKING REAGENT; ONCOPROTEIN; PEPTIDE; PEPTIDE FRAGMENT;

ALPHA HELIX; AMINO ACID SEQUENCE; BIOLOGICAL ACTIVITY; CELL MEMBRANE PERMEABILITY; CELL TRANSPORT; CROSS REACTION; HYDROPHILICITY; HYDROPHOBICITY; IN VIVO STUDY; MEDICAL RESEARCH; PEPTIDE SYNTHESIS; PROTEIN ANALYSIS; PROTEIN DEGRADATION; PROTEIN PROTEIN INTERACTION; PROTEIN STRUCTURE; PROTEIN TARGETING; REVIEW; RING OPENING; SOLUBILITY; SOLUBILIZATION; STRUCTURE ACTIVITY RELATION; ANALOGS AND DERIVATIVES; ANIMAL; CHEMISTRY; HUMAN; METABOLISM; PROTEIN SECONDARY STRUCTURE; PROTEIN UNFOLDING;

ALANINE; ANIMALS; BIOMEDICAL RESEARCH; CROSS-LINKING REAGENTS; HUMANS; HYDROCARBONS; PEPTIDE FRAGMENTS; PEPTIDES; PROTEIN STRUCTURE, SECONDARY; PROTEIN UNFOLDING; PROTEOLYSIS; PROTO-ONCOGENE PROTEINS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84901681947     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm4011675     Document Type: Review

References (69)

1. Bock, J. E.; Gavenonis, J.; Kritzer, J. A. Getting in shape: controlling peptide bioactivity and bioavailability using conformational constraints ACS Chem. Biol. 2013, 8, 488-499
2. Guarracino, D. A.; Bullock, B. N.; Arora, P. S. Mini review: protein-protein interactions in transcription: a fertile ground for helix mimetics Biopolymers 2011, 95, 1-7
3. Presta, L. G.; Rose, G. D. Helix signals in proteins Science 1988, 240, 1632-1641
4. Klingler, T. M.; Brutlag, D. L. Discovering structural correlations in alpha-helices Protein Sci. 1994, 3, 1847-1857
5. Balaram, P. Non-standard amino acids in peptide design and protein engineering Curr. Opin. Struct. Biol. 1992, 2, 845-851
6. Karle, I. L.; Flippen-Anderson, J. L.; Uma, K.; Balaram, P. Apolar peptide models for conformational heterogeneity, hydration, and packing of polypeptide helices: crystal structure of hepta-and octapeptides containing alpha-aminoisobutyric acid Proteins 1990, 7, 62-73
7. Jackson, D. Y.; King, D. S.; Chmielewski, J.; Singh, S.; Schultz, P. G. General approach to the synthesis of short.alpha.-helical peptides J. Am. Chem. Soc. 1991, 113, 9391-9392
8. Bracken, C.; Gulyas, J.; Taylor, J. W.; Baum, J. Synthesis and nuclear-magnetic-resonance structure determination of an alpha-helical, bicyclic, lactam-bridged hexapeptide J. Am. Chem. Soc. 1994, 116, 6431-6432
9. Chen, S. T.; Chen, H. J.; Yu, H. M.; Wang, K. T. Facile synthesis of a short peptide with a side-chain-constrained structure J. Chem. Res., Synop. 1993, 228-229
10. Phelan, J. C.; Skelton, N. J.; Braisted, A. C.; McDowell, R. S. A general method for constraining short peptides to a helical conformation J. Am. Chem. Soc. 1997, 119, 455-460
11. Schafmeister, C. E.; Po, J.; Verdine, G. L. An all-hydrocarbon cross-linking system for enhancing the helicity and metabolic stability of peptides J. Am. Chem. Soc. 2000, 122, 5891-5892
12. Blackwell, H. E.; Grubbs, R. H. Highly efficient synthesis of covalently cross-linked peptide helices by ring-closing metathesis Angew. Chem., Int. Ed. 1994, 37, 3281-3284
13. Whelan, J. Stapled peptide induces cancer cell death Drug Discovery Today 2004, 9, 907
14. Walker, W. L.; Kopka, M. L.; Dickerson, R. E.; Goodsell, D. S. Design of stapled DNA-minor-groove-binding molecules with a mutable atom simulated annealing method J. Comput.-Aided Mol. Des. 1997, 11, 539-546
15. Barthe, P.; Rochette, S.; Vita, C.; Roumestand, C. Synthesis and NMR solution structure of an alpha-helical hairpin stapled with two disulfide bridges Protein Sci. 2000, 9, 942-955
16. Blackwell, H. E.; Sadowsky, J. D.; Howard, R. J.; Sampson, J. N.; Chao, J. A.; Steinmetz, W. E.; O'Leary, D. J.; Grubbs, R. H. Ring-closing metathesis of olefinic peptides: design, synthesis, and structural characterization of macrocyclic helical peptides J. Org. Chem. 2001, 66, 5291-5302
17. Letai, A.; Bassik, M. C.; Walensky, L. D.; Sorcinelli, M. D.; Weiler, S.; Korsmeyer, S. J. Distinct BH3 domains either sensitize or activate mitochondrial apoptosis, serving as prototype cancer therapeutics Cancer Cell 2002, 2, 183-192
18. Walensky, L. D.; Kung, A. L.; Escher, I.; Malia, T. J.; Barbuto, S.; Wright, R. D.; Wagner, G.; Verdine, G. L.; Korsmeyer, S. J. Activation of apoptosis in vivo by a hydrocarbon-stapled BH3 helix Science 2004, 305, 1466-1470
19. Williams, R. M.; Sinclair, P. J.; Zhai, D.; Chen, D. Practical asymmetric syntheses of.alpha.-amino acids through carbon-carbon bond constructions on electrophilic glycine templates J. Am. Chem. Soc. 1988, 110, 1547-1557
20. Williams, R. M.; Sinclair, P. J.; DeMong, D. E.; Chen, D.; Zhai, D. Asymmetric Synthesis of N-tert-butoxycarbonyl alpha-amino acids: synthesis of (5 S,6 R)-4-tert-butoxycarbonyl-5,6-diphenylmorpholin-2-one Org. Synth. 2003, 80, 18-30
21. Williams, R. M.; Im, M. N. Asymmetric synthesis of monosubstituted and alpha, alpha-disubstituted amino acids via diastereoselective glycine enolate alkylations J. Am. Chem. Soc. 1991, 113, 9276-9286
22. Belokon, Y.; Tararov, V.; Maleev, V.; Savel'eva, T.; Ryzhov, M. Improved procedures for the synthesis of (S)-2-[ N-(N'-benzylprolyl)amino]benzophenone (BPB) and Ni(II) complexes of Schiff's bases derived from BPB and amino acids Tetrahedron: Asymmetry 1998, 9, 4249-4252
23. Qiu, W.; Soloshonok, V.; Cai, C.; Tang, X.; Hruby, V. Convenient, large-scale asymmetric synthesis of enantiomerically pure trans-cinnamylglycine and-α-alanine Tetrahedron 2000, 56, 2577-2582
24. Bird, G. H.; Bernal, F.; Pitter, K.; Walensky, L. D. Synthesis and biophysical characterization of stabilized alpha-helices of BCL-2 domains Methods Enzymol. 2008, 446, 369-386
25. Bird, G. H.; Crannell, C. W.; Walensky, L. D. Chemical synthesis of hydrocarbon-stapled peptides for protein interaction research and therapeutic targeting Curr. Protoc. Chem. Biol. 2011, 3, 99-117
26. Kim, Y. W.; Grossmann, T. N.; Verdine, G. L. Synthesis of all-hydrocarbon stapled alpha-helical peptides by ring-closing olefin metathesis Nat. Protoc. 2011, 6, 761-771
27. Braun, C. R.; Mintseris, J.; Gavathiotis, E.; Bird, G. H.; Gygi, S. P.; Walensky, L. D. Photoreactive stapled BH3 peptides to dissect the BCL-2 family interactome Chem. Biol. 2010, 17, 1325-1333
28. Gavathiotis, E.; Suzuki, M.; Davis, M. L.; Pitter, K.; Bird, G. H.; Katz, S. G.; Tu, H. C.; Kim, H.; Cheng, E. H.; Tjandra, N.; Walensky, L. D. BAX activation is initiated at a novel interaction site Nature 2008, 455, 1076-1081
29. LaBelle, J. L.; Katz, S. G.; Bird, G. H.; Gavathiotis, E.; Stewart, M. L.; Lawrence, C.; Fisher, J. K.; Godes, M.; Pitter, K.; Kung, A. L.; Walensky, L. D. A stapled BIM peptide overcomes apoptotic resistance in hematologic cancers J. Clin. Invest. 2012, 122, 2018-2031
30. Stewart, M. L.; Fire, E.; Keating, A. E.; Walensky, L. D. The MCL-1 BH3 helix is an exclusive MCL-1 inhibitor and apoptosis sensitizer Nat. Chem. Biol. 2010, 6, 595-601
31. Walensky, L. D.; Pitter, K.; Morash, J.; Oh, K. J.; Barbuto, S.; Fisher, J.; Smith, E.; Verdine, G. L.; Korsmeyer, S. J. A stapled BID BH3 helix directly binds and activates BAX Mol. Cell 2006, 24, 199-210
32. Bird, G. H.; Madani, N.; Perry, A. F.; Princiotto, A. M.; Supko, J. G.; He, X.; Gavathiotis, E.; Sodroski, J. G.; Walensky, L. D. Hydrocarbon double-stapling remedies the proteolytic instability of a lengthy peptide therapeutic Proc. Natl. Acad. Sci. U.S.A. 2010, 107, 14093-14098
33. Bernal, F.; Tyler, A. F.; Korsmeyer, S. J.; Walensky, L. D.; Verdine, G. L. Reactivation of the p53 tumor suppressor pathway by a stapled p53 peptide J. Am. Chem. Soc. 2007, 129, 2456-2457
34. Joseph, T. L.; Lane, D.; Verma, C. S. Stapled peptides in the p53 pathway: computer simulations reveal novel interactions of the staples with the target protein Cell Cycle 2010, 9, 4560-4568
35. Joseph, T. L.; Lane, D. P.; Verma, C. S. Stapled BH3 peptides against MCL-1: mechanism and design using atomistic simulations PLoS One 2012, 7, e43985
36. Bhattacharya, S.; Zhang, H.; Cowburn, D.; Debnath, A. K. Novel structures of self-associating stapled peptides Biopolymers 2012, 97, 253-264
37. Bhattacharya, S.; Zhang, H.; Debnath, A. K.; Cowburn, D. Solution structure of a hydrocarbon stapled peptide inhibitor in complex with monomeric C-terminal domain of HIV-1 capsid J. Biol. Chem. 2008, 283, 16274-16278
38. Moldoveanu, T.; Grace, C. R.; Llambi, F.; Nourse, A.; Fitzgerald, P.; Gehring, K.; Kriwacki, R. W.; Green, D. R. BID-induced structural changes in BAK promote apoptosis Nat. Struct. Mol. Biol. 2013, 20, 589-597
39. Baek, S.; Kutchukian, P. S.; Verdine, G. L.; Huber, R.; Holak, T. A.; Lee, K. W.; Popowicz, G. M. Structure of the stapled p53 peptide bound to Mdm2 J. Am. Chem. Soc. 2012, 134, 103-106
40. Grossmann, T. N.; Yeh, J. T.; Bowman, B. R.; Chu, Q.; Moellering, R. E.; Verdine, G. L. Inhibition of oncogenic Wnt signaling through direct targeting of beta-catenin Proc. Natl. Acad. Sci. U.S.A. 2012, 109, 17942-17947
41. 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.; Sawyer, T. K. Stapled alpha-helical peptide drug development: a potent dual inhibitor of MDM2 and MDMX for p53-dependent cancer therapy Proc. Natl. Acad. Sci. U.S.A. 2013, 110, E3445-E3454
42. Bernal, F.; Wade, M.; Godes, M.; Davis, T. N.; Whitehead, D. G.; Kung, A. L.; Wahl, G. M.; Walensky, L. D. A stapled p53 helix overcomes HDMX-mediated suppression of p53 Cancer Cell 2010, 18, 411-422
43. Takada, K.; Zhu, D.; 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.; Carrasco, D. R. Targeted disruption of the BCL9/beta-catenin complex inhibits oncogenic Wnt signaling Sci. Transl. Med. 2012, 4, 148ra117
44. van den Berg, A.; Dowdy, S. F. Protein transduction domain delivery of therapeutic macromolecules Curr. Opin. Biotechnol. 2011, 22, 888-893
45. Hirose, H.; Takeuchi, T.; Osakada, H.; Pujals, S.; Katayama, S.; Nakase, I.; Kobayashi, S.; Haraguchi, T.; Futaki, S. Transient focal membrane deformation induced by arginine-rich peptides leads to their direct penetration into cells Mol. Ther. 2012, 20, 984-993
46. Edwards, A. L.; Gavathiotis, E.; LaBelle, J. L.; Braun, C. R.; Opoku-Nsiah, K. A.; Bird, G. H.; Walensky, L. D. Multimodal interaction with BCL-2 family proteins underlies the pro-apoptotic activity of PUMA BH3 Chem. Biol. 2013, 20, 888-902
47. Commisso, C.; Davidson, S. M.; Soydaner-Azeloglu, R. G.; Parker, S. J.; Kamphorst, J. J.; Hackett, S.; Grabocka, E.; Nofal, M.; Drebin, J. A.; Thompson, C. B.; Rabinowitz, J. D.; Metallo, C. M.; Vander Heiden, M. G.; Bar-Sagi, D. Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells Nature 2013, 497, 633-637
48. 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.; Lane, D. P. Stapled peptides with improved potency and specificity that activate p53 ACS Chem. Biol. 2013, 8, 506-512
49. Danial, N. N.; Walensky, L. D.; Zhang, C. Y.; Choi, C. S.; Fisher, J. K.; Molina, A. J.; 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.; Korsmeyer, S. J. Dual role of proapoptotic BAD in insulin secretion and beta cell survival Nat. Med. 2008, 14, 144-153
50. Hao, Y.; Wang, C.; Cao, B.; Hirsch, B. M.; Song, J.; Markowitz, S. D.; Ewing, R. M.; Sedwick, D.; Liu, L.; Zheng, W.; Wang, Z. Gain of interaction with IRS1 by p110alpha-helical domain mutants is crucial for their oncogenic functions Cancer Cell 2013, 23, 583-593
51. Moellering, R. E.; Cornejo, M.; Davis, T. N.; Del Bianco, C.; Aster, J. C.; Blacklow, S. C.; Kung, A. L.; Gilliland, D. G.; Verdine, G. L.; Bradner, J. E. Direct inhibition of the NOTCH transcription factor complex Nature 2009, 462, 182-188
52. Kim, W.; Bird, G. H.; Neff, T.; Guo, G.; Kerenyi, M. A.; Walensky, L. D.; Orkin, S. H. Targeted disruption of the EZH2-EED complex inhibits EZH2-dependent cancer Nat. Chem. Biol. 2013, 9, 643-650
53. Bautista, A. D.; Appelbaum, J. S.; Craig, C. J.; Michel, J.; Schepartz, A. Bridged beta(3)-peptide inhibitors of p53-hDM2 complexation: correlation between affinity and cell permeability J. Am. Chem. Soc. 2010, 132, 2904-2906
54. Cui, H. K.; Zhao, B.; Li, Y.; Guo, Y.; Hu, H.; Liu, L.; Chen, Y. G. Design of stapled alpha-helical peptides to specifically activate Wnt/beta-catenin signaling Cell Res. 2013, 23, 581-584
55. Gembarska, A.; Luciani, F.; Fedele, C.; Russell, E. A.; Dewaele, M.; Villar, S.; Zwolinska, A.; Haupt, S.; de Lange, J.; 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.; Marine, J. C. MDM4 is a key therapeutic target in cutaneous melanoma Nat. Med. 2012, 18, 1239-1247
56. Kim, Y. W.; Kutchukian, P. S.; Verdine, G. L. Introduction of all-hydrocarbon i,i+3 staples into alpha-helices via ring-closing olefin metathesis Org. Lett. 2010, 12, 3046-3049
57. Zhang, H.; Curreli, F.; Zhang, X.; Bhattacharya, S.; Waheed, A. A.; Cooper, A.; Cowburn, D.; Freed, E. O.; Debnath, A. K. Antiviral activity of alpha-helical stapled peptides designed from the HIV-1 capsid dimerization domain Retrovirology 2011, 8, 28
58. Zhang, H.; Zhao, Q.; Bhattacharya, S.; Waheed, A. A.; Tong, X.; Hong, A.; Heck, S.; Curreli, F.; Goger, M.; Cowburn, D.; Freed, E. O.; Debnath, A. K. A cell-penetrating helical peptide as a potential HIV-1 inhibitor J. Mol. Biol. 2008, 378, 565-580
59. Bechinger, B. Structure and functions of channel-forming peptides: magainins, cecropins, melittin and alamethicin J. Membr. Biol. 1997, 156, 197-211
60. Pitter, K.; Bernal, F.; Labelle, J.; Walensky, L. D. Dissection of the BCL-2 family signaling network with stabilized alpha-helices of BCL-2 domains Methods Enzymol. 2008, 446, 387-408
61. Okamoto, T.; Zobel, K.; Fedorova, A.; Quan, C.; Yang, H.; Fairbrother, W. J.; Huang, D. C.; Smith, B. J.; Deshayes, K.; Czabotar, P. E. Stabilizing the pro-apoptotic BimBH3 helix (BimSAHB) does not necessarily enhance affinity or biological activity ACS Chem. Biol. 2013, 8, 297-302
62. Gavathiotis, E.; Reyna, D. E.; Davis, M. L.; Bird, G. H.; Walensky, L. D. BH3-triggered structural reorganization drives the activation of proapoptotic BAX Mol. Cell 2010, 40, 481-492
63. Bird, G. H.; Gavathiotis, E.; Labelle, J. L.; Katz, S. G.; Walensky, L. D. Distinct BimBH3 (BimSAHB) stapled peptides for structural and cellular studies. ACS Chem. Biol. [Online early access]. DOI: 10.1021/cb4003305. Published Online" Dec 20, 2013.
64. Long, Y. Q.; Huang, S. X.; Zawahir, Z.; Xu, Z. L.; Li, H.; Sanchez, T. W.; Zhi, Y.; De Houwer, S.; Christ, F.; Debyser, Z.; Neamati, N. Design of cell-permeable stapled peptides as HIV-1 integrase inhibitors J. Med. Chem. 2013, 56, 5601-5612
65. Sviridov, D. O.; Ikpot, I. Z.; Stonik, J.; Drake, S. K.; Amar, M.; Osei-Hwedieh, D. O.; Piszczek, G.; Turner, S.; Remaley, A. T. Helix stabilization of amphipathic peptides by hydrocarbon stapling increases cholesterol efflux by the ABCA1 transporter Biochem. Biophys. Res. Commun. 2011, 410, 446-451
66. Platt, R. J.; Han, T. S.; Green, B. R.; Smith, M. D.; Skalicky, J.; Gruszczynski, P.; White, H. S.; Olivera, B.; Bulaj, G.; Gajewiak, J. Stapling mimics noncovalent interactions of gamma-carboxyglutamates in conantokins, peptidic antagonists of N-methyl-d-aspartic acid receptors J. Biol. Chem. 2012, 287, 20727-20736
67. Green, B. R.; Klein, B. D.; Lee, H. K.; Smith, M. D.; Steve White, H.; Bulaj, G. Cyclic analogs of galanin and neuropeptide Y by hydrocarbon stapling Bioorg. Med. Chem. 2013, 21, 303-310
68. Cui, H. K.; Qing, J.; Guo, Y.; Wang, Y. J.; Cui, L. J.; He, T. H.; Zhang, L.; Liu, L. Stapled peptide-based membrane fusion inhibitors of hepatitis C virus Bioorg. Med. Chem. 2013, 21, 3547-3554
69. Szlyk, B.; Braun, C. R.; Ljubicic, S.; Patton, E.; Bird, G. H.; Osundiji, M. A.; Matschinsky, F. M.; Walensky, L. D.; Danial, N. N. A phospho-BAD BH3 helix activates glucokinase by a mechanism distinct from that of allosteric activators Nat. Struct. Mol. Biol. 2014, 21, 36-42