Inhibition of mammalian collagenases by thiol-containing peptides.

Abstract:

:The following thiol-containing peptide analogues of the carboxyl side of the collagenase-sensitive bond of collagen were synthesized and tested as inhibitors of collagenases partially purified from homogenates of rabbit V-2 tumor and culture medium of pig synovium: HSCH2CH(CH3)CO-Ala-OEt (I), HSCH2CH(CH2Ph)CO-Ala-OEt (II), HSCH2CH[CH2CH(CH3)2]CO-Ala-OEt (III); HSCH2 CH-[CH2CH(CH3)2]CO-Ala-Gly-OEt (IV); HSCH2CH[CH2CH(CH3)2]CO-Ala-Gly-Gln (V). The compounds are listed in order of their inhibitory potency when assayed with nonfibrillar-acid-soluble calf skin collagen at pH 7.6, 35 degrees C. The best inhibitor (III) gave 50% inhibition between 1 and 4 microM. II was a competitive inhibitor with a Ki value of 75 microM. The enzymes preferred an isobutyl side chain at the 2-carbon position, and, where tested (III, IV), did not discriminate strongly between stereoisomers at the chiral 2-carbon. Increasing the length of the inhibitor did not markedly increase potency.

journal_name

J Cell Biochem

authors

Gray RD,Miller RB,Spatola AF

doi

10.1002/jcb.240320108

subject

Has Abstract

pub_date

1986-01-01 00:00:00

pages

71-7

issue

1

eissn

0730-2312

issn

1097-4644

journal_volume

32

pub_type

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