Aziridine-mediated ligation and site-specific modification of unprotected peptides

Journal of the American Chemical Society

Volumn 133, Issue 50, 2011, Pages 20033-20035

  Dyer, Frank Brock ^a   Park, Chung Min ^a   Joseph, Ryan ^a   Garner, Philip ^a  

^a WASHINGTON STATE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

N-TERMINALS; NUCLEOPHILIC RING-OPENING; REGIO-SELECTIVE; SIDE-CHAINS; SITE-SPECIFIC MODIFICATIONS; STEREO-SELECTIVE; THIOACIDS;

AMINO ACIDS; IONIC LIQUIDS;

PEPTIDES;

AZIRIDINE; COPPER; PEPTIDE; UNCLASSIFIED DRUG; UNPROTECTED PEPTIDE;

ARTICLE; CHEMICAL MODIFICATION; CHEMICAL STRUCTURE; LIGATION; RING OPENING; SITE SPECIFIC MODIFICATION; STEREOCHEMISTRY; SYNTHESIS;

AZIRIDINES; PEPTIDES;

EID: 83755171494     PISSN: 00027863     EISSN: 15205126     Source Type: Journal    
DOI: 10.1021/ja207133t     Document Type: Article

References (31)

1. Tam, J. P.; Xu, J.; Eom, K. D. Biopolymers 2001, 60, 194-205
2. Nilsson, B. L.; Soellner, M. B.; Raines, R. T. Annu. Rev. Biophys. Biomol. Struct. 2005, 34, 91-118
3. Hackenberger, C. P. R.; Schwarzer, D. Angew. Chem., Int. Ed. 2008, 47, 10030-10074
4. Kent, S. B. H. Chem. Soc. Rev. 2009, 38, 338-351
5. Tam, J. P.; Yu, Q. Biopolymers 1998, 46, 319-327
6. Offer, J.; Boddy, C. N. C.; Dawson, P. E. J. Am. Chem. Soc. 2002, 124, 4642-4646
7. Wu, B.; Chen, J.; Warren, J. D.; Chen, G.; Hua, Z.; Danishefsky, S. J. Angew. Chem., Int. Ed. 2006, 45, 4116-4125
8. Botti, P.; Tchertchian, S. WO/2006/133962, 2006.
9. Crich, D.; Banerjee, A. J. Am. Chem. Soc. 2007, 129, 10064-10065
10. Payne, R. J.; Fichet, S.; Greenberg, W. A.; Wong, C.-H. Angew. Chem., Int. Ed. 2008, 47, 4411-4415
11. Okamoto, R.; Kajihara, Y. Angew. Chem., Int. Ed. 2008, 47, 5402-5406
12. Haase, C.; Rohde, H.; Seitz, O. Angew. Chem., Int. Ed. 2008, 47, 6807-6810
13. Chen, J.; Wan, Q.; Yuan, Y.; Zhu, J.; Danishefsky, S. J. Angew. Chem., Int. Ed. 2008, 47, 8521-8524
14. Bennett, C. S.; Dean, S. M.; Payne, R. J.; Ficht, S.; Brik, A.; Wong, C.-H. J. Am. Chem. Soc. 2008, 130, 11945-11952
15. Yang, R.; Pasunooti, K. K.; Li, F.; Liu, X.-W.; Liu, C.-F. J. Am. Chem. Soc. 2009, 131, 13592-13593
16. Harpaz, Z.; Siman, P.; Kumar, K. S. A.; Brik, A. ChemBioChem 2010, 11, 1232-1235
17. Chen, J.; Wang, P; Zhu, J.; Wan, Q.; Danishefsky, S. J. Tetrahedron 2010, 66, 2277-2283
18. Shang, S.; Tan, Z.; Dong, S.; Danishefsky, S. J. J. Am. Chem. Soc. 2011, 133, 10784-10786
19. Danishefsky has reported the HOBt-mediated oxidative coupling of peptide thioacids and free N-terminal peptides. This method is not compatible with unprotected sidechain amines. Wang., P.; Danishefsky, S. J. J. Am. Chem. Soc. 2010, 132, 17045-17051
20. Okawa, K.; Nakajima, K. Biopolymers 1981, 20, 1811-1821
21. Korn, A.; Rudolph-Böhner, S.; Moroder, L. Tetrahedron 1994, 50, 1717-1730
22. Galonic, D. P.; Ide, N. D.; van der Donk, W. A.; Gin, D. Y. J. Am. Chem. Soc. 2005, 127, 7359-7369
23. Shao, H.; Jiang, X.; Gantzel, P.; Goodman, M. Chem. Biol. 1994, 1, 231-234
24. The C2-selective opening of NH aziridine-2-carbonyl-terminated peptides (formed in situ from β-bromoalanylpeptides) by peptide thioacids to give a β-peptide linkage (after S-to N -acyl transfer) was originally observed by Tam et al.: Tam, J. P.; Lu, Y. A.; Liu, C. F.; Shao, J. Proc. Natl. Acad. Sci. U.S.A. 1995, 92, 12485-12489
25. Recently, a convergent synthesis of protected peptidomimetics via the coupling of protected peptide thioacids and protected 2-aziridinylmethylpeptides was reported: Assem, N.; Natarajan, A.; Yudin, A. K. J. Am. Chem. Soc. 2010, 132, 10986-10987
26. Schwabacher, A. W.; Bychowski, R. A. Tetrahedron Lett. 1992, 33, 21-24
27. Blake, J. Int. J. Pept. Protein Res. 1981, 17, 273-274
28. Blake, J.; Li, C. H. Proc. Natl. Acad. Sci. U.S.A. 1981, 78, 4055-4058
29. 6, is known to promote the N-acylation of primary amines via dithioacids: Liu, R.; Orgel, L. E. Nature 1997, 389, 52-54
30. Thioacid 8 was prepared from commercially available Ac-Phe-OH [(1) NHS, DCC, DCM, rt, 4 h; (2) NaHS, MeOH, 63% yield] using a known method: Goldstein, A. S.; Gelb, M. H. Tetrahedron Lett. 2000, 41, 2797-2800
31. MS analysis of this coupling reaction indicated predominant formation of a disulfide corresponding to intermediate 12, which implies that the free thiol may be undergoing an in situ protection. Reductive disulfide cleavage likely occurs during the workup with aqueous NaSH, which can act as a reducing agent. Minor products emanating from perthioester intermediates were also detected. See: Liu, C. F.; Rao, C.; Tam, J. P. Tetrahedron Lett. 1996, 37, 933-936