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.
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Authors | R D Gray, R B Miller, A F Spatola |
Journal | Journal of cellular biochemistry
(J Cell Biochem)
Vol. 32
Issue 1
Pg. 71-7
( 1986)
ISSN: 0730-2312 [Print] United States |
PMID | 3021790
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Peptide Fragments
- Sulfhydryl Compounds
- Collagen
- Microbial Collagenase
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Topics |
- Animals
- Collagen
- Microbial Collagenase
(antagonists & inhibitors)
- Neoplasms, Experimental
(enzymology)
- Peptide Fragments
(pharmacology)
- Rabbits
- Stereoisomerism
- Structure-Activity Relationship
- Sulfhydryl Compounds
(pharmacology)
- Swine
- Synovial Membrane
(enzymology)
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