SYNTHESIS OF N-GLYOXYLYL PEPTIDES AND THEIR IN-VITRO EVALUATION AS HIV-1 PROTEASE INHIBITORS

A series of novel synthetic peptides containing an N-terminal glyoxyly l function (CHOCO-) have been tested as inhibitors of HIV-1 protease. The N-glyoxylyl peptide CHOCO-Pro-Ile-Val-NH2, which fulfills the spec ificity requirements of the MA/CA protease cleavage site together with the criteria of transition state analogue of the catalyzed reaction, was found to be a moderate competitive inhibitor although favorable in teractions were visualized between its hydrated form and the catalytic aspartates using molecular modeling. Increasing the length of the pep tide sequence led to compounds acting only as substrates. (C) 1997 Els evier Science Ltd.