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J Med Chem. 1993 Dec 24;36(26):4293-301.

Inhibition of matrix metalloproteinases by N-carboxyalkyl peptides.

Author information

1
Department of Medicinal Chemical Research, Merck Research Laboratories, Rahway, New Jersey 07065-0900.

Abstract

An extensive study of the requirements for effective binding of N-carboxyalkyl peptides to human stromelysin, collagenase, and to a lesser extent, gelatinase A has been investigated. These efforts afforded inhibitors generally in the 100-400 nM range for these matrix metalloproteinases. The most significant increase in potency was obtained with the introduction of a beta-phenylethyl group at the P1' position, suggesting a small hydrophobic channel into the S1' subsite of stromelysin. One particular compound, N-[1(R)-carboxyethyl]-alpha(S)-(2-phenylethyl)glycyl-L-leucine,N- phenylamide (79a), is relatively selective for rabbit stromelysin with a K(i) = 6.5 nM and may prove useful for elucidating the role of endogenously-produced stromelysin in lapine models of tissue degradation.

PMID:
8277511
DOI:
10.1021/jm00078a019
[Indexed for MEDLINE]

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