INTERLEUKIN-1-BETA CONVERTING-ENZYME - SYNTHESIS OF HYDROXYETHYL DIPEPTIDE SURROGATE-CONTAINING COMPOUNDS AS POTENTIAL ICE INHIBITORS

A series of compounds containing a hydroxyethyl-based dipeptide surrog ate have been prepared as probes to evaluate the possibility of ICE be ing an aspartic protease. The aldehyde t-BocAsp(beta-t-butyl)H reacted with the organochromium species derived from phenethyl bromide and Cr Cl2 to give the expected addition product. Lactonization, reprotection of the amine and oxidation with RuCl3 gave the two protected dipeptid e surrogates 7a and 7b. These were incorporated into tetra-, penta- an d hexapeptide-like molecules and evaluated as inhibitors of the enzyme . The failure of these compounds to inhibit ICE indicated that this en zyme was very unlikely to be an aspartic protease.