Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Actinonin is a pseudopeptide antibiotic which inhibits collagenase at micromolar concentrations [10]. In this study, Actinonin analogs were tested to investigate "structure/activity" relationships for this class of molecule. The results indicate that distance between the hydroxamate carbonyl group and that of the first amide bond is important, since increasing this distance by a methylene group, decreases inhibition by a factor of 100. The amide bonds of this inhibitor must be in the peptide bond orientation. Different N terminal amide derivatives and different hydrophobic substituents adjacent to the hydroxamate residue, had little effect on inhibitory activity. However, in this series of molecules, two hydrophobic groups separated by an amide bond seem to be necessary for potent inhibition.
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PMID:[Inhibition of synovial collagenase by actinonin. Study of structure/activity relationship]. 253 94

Snake envenomation is a relatively neglected significant world health problem, designated an orphan disease by the WHO. While often effective, antivenins are insufficient. Could another approach greatly aid inhibition of the venom toxins? New fluorescent substrates for measuring protease activity in microplate assays suitable for high throughput screening were tested and found reproducible with snake venom. Representative North American venoms showed relatively strong proteinase and collagenase, but weaker elastase activities. Caseinolytic activity is inhibited by the nonspecific proteinase inhibitor 1,10-phenanthroline and by EDTA, as is collagenase activity, consistent with the action of metalloproteinases. Both general protease and collagenase assays CV average 3%, and Km measured were above normal working conditions. Using a library of anti -proteinase compounds with multiple venoms revealed high inhibitor activity by three agents with known multiple metalloproteinase inhibitor activity (Actinonin, GM6001, and NNGH), which incidentally supports the concept that much of the degradative activity of certain venoms is due to metalloproteinases with collagenase activity. These results together support the use of microplate proteinase assays, particularly this collagenase assay, in future drug repurposing studies leading to the development of new treatments for those envenomations that have a major proteolytic component in their pathophysiology.
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PMID:Microplate fluorescence protease assays test the inhibition of select North American snake venoms' activities with an anti-proteinase library. 2613 May 21