• W Hornebeck, E Moczar, J Szecsi, and L Robert.
• Biochem. Pharmacol. 1985 Sep 15; 34 (18): 3315-21.

AbstractPeptide sequences which fit the extended binding sites of porcine pancreatic elastase and human leukocyte elastase were covalently coupled to oleic acid. These compounds behave as competitive inhibitors towards both elastases. The coupling of fatty acid moiety to the peptide greatly decreases its inhibitor constant (Ki) vs human leukocyte elastase (Ki for Oleoyl(Ala)2ProValine: 3.0 (10(-6)M). It is less active on porcine pancreatic elastase (Ki for Oleoyl(Ala)2ProAlanine: 3.8 10(-4)M). The modifications of the carboxylic end group of the peptide to an aldehyde further greatly enhanced the inhibition capacity of the compound towards leukocyte elastase (Ki for Oleoyl(Ala)2ProAlaninal: 0.7 microM). Oleoyl peptide derivatives were seen to bind in a saturable fashion to purified insoluble elastin, and decreased the susceptibility of the macromolecule to hydrolysis by both pancreatic and leukocyte elastases. As stoichiometric quantities of elastase (vs inhibitor) could not desorb 3H-oleoyl(Ala)2Pro-Val bound to insoluble elastin, it is postulated that oleoyl peptide derivatives may act as bifunctional agents. This contention was further strengthened by the comparison of the adsorption curves of elastase to untreated insoluble elastin and elastin saturated with oleoyl peptide derivatives respectively. It was shown finally that Oleoyl(Ala)2Pro-Valine was also capable of inhibiting elastases in their adsorbed form to insoluble elastin.

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