The development of hydrazide γ-Turn mimetics

Tetrahedron Letters

Volumn 38, Issue 40, 1997, Pages 6961-6964

  Ferguson, Mark D ^a   Meara, Joseph P ^a   Nakanishi, Hiroshi ^a   Lee, Min S ^a   Kahna, Michael ^a,b  

^a Molecumetics Ltd   (United States)

^b UNIVERSITY OF WASHINGTON   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLOPEPTIDE; MALFORMIN; PENTAPEPTIDE; UNCLASSIFIED DRUG;

ARTICLE; COMPUTER SECURITY; DRUG DESIGN; DRUG STRUCTURE; DRUG SYNTHESIS; IN VITRO STUDY; MOLECULAR DYNAMICS; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; REACTION ANALYSIS;

EID: 0030867016     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(97)01664-X     Document Type: Article

References (18)

1. Nakanishi, H.; Kahn, M. In The Practice of Medicinal Chemistry; Wermuth, C.G.; Ed.; Academic: London, 1996; pp 571-590.
2. Kaiser, E. T.; Kezdy, F. J. Proc. Natl. Acad. Sci. U.S.A. 1983, 80, 1137.
3. A γ-turn is defined by a hydrogen bond formation between the CO group of residue i and NH group of residue i +2. Two types of γ-turns exist, the classical γ-turn, with the middle residue (φ, ψ) values in the range of (70 to 95, -75 to -45), and the inverse γ-turn in the range of (-95 to -70, 45 to 75). See Rose, G.D.; Gierashch, L. M.; Smith, J. A. Advances in Protein Chemistry 1985, 37, 1, and Alkorta, I.; Suarez, M. L.; Herranz, R.; Gonzalez-Muniz, R.; Garcia-Lopez, M. T. J. Mol. Model. 1996, 2, 16.
4. A γ-turn is defined by a hydrogen bond formation between the CO group of residue i and NH group of residue i +2. Two types of γ-turns exist, the classical γ-turn, with the middle residue (φ, ψ) values in the range of (70 to 95, -75 to -45), and the inverse γ-turn in the range of (-95 to -70, 45 to 75). See Rose, G.D.; Gierashch, L. M.; Smith, J. A. Advances in Protein Chemistry 1985, 37, 1, and Alkorta, I.; Suarez, M. L.; Herranz, R.; Gonzalez-Muniz, R.; Garcia-Lopez, M. T. J. Mol. Model. 1996, 2, 16.
5. Sato, M.; Lee, J. Y. H.; Nakanishi, H.; Johnson, M. E.; Chrusciel, R. A.; Kahn, M. Biochem. Biophys. Res. Commun. 1992, 187, 999.
6. Curtis, R. W. Science 1958, 128, 661.
7. Sugawara, F.; Kim, K. W.; Uzawa, J.; Yoshida, S.; Takahashi, N.; Curtis, R. W. Tetrahedron Lett. 1990, 31, 4337.
8. McDonald, N. Q.; Lapatto, R.; Murray-Rust, J.; Gunning, J.; Wlodawer, A.; Blundell, T. L. Nature 1991, 354, 411.
9. Sapporo Breweries JP 5262663.
10. Yankner, B. A.; Caceres, A.; Duffy, L. K. Proc. Natl. Acad. Sci. U.S.A. 1990, 87, 9020.
11. Constructed in Macromodel (Columbia University). A series of 5000 step Monte Carlo conformational searches were carried out in a simulated water environment by GB/SA solvation model with MM2/MMOD force field using Batchmin 3.5 (Columbia University). A RMSD at 9 atom positions was 0.12 Å with the idealized classical γ-turn, and a RMSD at 6 atom positions was 0.57 Å with the idealized type I' β-turn.
12. The RMSD, 0.17 Å, of the γ-turn templates were compared with ideal γ-turns and the global minimum conformation of abbreviated malformin were obtained at 9 atom positions: Cα(i), C(i), N(i + 1), Cα(i +1), C(i +1), O(i + 1), Cβ(i +1), N(i + 2), and Cα(i + 2).
13. Gardner, B.; Nakanishi, H.; Kahn, M. Tetrahedron 1993, 49, 3433.
14. Hoffman, R. V.; Kim, H-O. Tetrahedron Lett. 1990, 31, 2953.
15. Kim, H-O., Gardner, B., Kahn, M. Tetrahedron Lett. 1995, 36, 6013.
16. A strong ROE from the acetate hydrogens to the hydrazine hydrogen supports the uncyclized product. This interaction is not present in γ-turn 1a.
17. A Varian Unity 500 MHz NMR was used for all of the experiments.
18. Dyson, H. J.; Rance, M.; Houghten, R. A.; Learner, R. A.; Wright, P. E. J. Mol. Biol. 1988, 201, 161.