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Inhibition of mammalian collagenases by thiol‐containing peptides
Author(s) -
Gray Robert D.,
Miller Robert B.,
Spatola Arno F.
Publication year - 1986
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.240320108
Subject(s) - thiol , collagenase , chemistry , biochemistry , microbiology and biotechnology , biology , enzyme
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: HSCH 2 CH(CH 3 )CO‐Ala‐OEt (I), HSCH 2 CH‐(CH 2 Ph)CO‐Ala‐OEt (II), HSCH 2 CH[CH 2 CH(CH 3 ) 2 ]CO‐Ala‐OEt (III); HSCH 2 , CH‐[CH 2 CH(CH 3 ) 2 ]CO‐Ala‐Gly‐OEt (IV); HSCH 2 CH[CH 2 CH(CH 3 ) 2 ]CO‐Ala‐Gly‐Gln (V). The compounds are listed in order of their inhibitory potency when assayed with nonfibrillar‐acid‐soluble calfskin collagen at pH 7.6, 35°C. The best inhibitor (III) gave 50% inhibition between 1 and 4 μM. II was a competitive inhibitor with a K i value of 75 μM. 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.