[Inhibition of synovial collagenase by actinonin. Study of structure/activity relationship].
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.
Lelièvre
Y
Y
Rhône-Poulenc Santé, Centre de Recherche de Vitry, Vitry-sur-Seine, France.
Bouboutou
R
R
Boiziau
J
J
Cartwright
T
T
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D003864:Depression, Chemical; D006877:Hydroxamic Acids / Q000494:pharmacology; D003012:Microbial Collagenase / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013552:Swine; D013582:Synovial Fluid / Q000201:enzymology*
D000900:Anti-Bacterial Agents; D006877:Hydroxamic Acids; D003012:Microbial Collagenase; C010531:actinonin
Inhibition de la collagénase synoviale par l'actinonine. Etude de relations structure/activité.