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 glyoxylyl function (CHOCO-) have been tested as inhibitors of HIV-1 protease. The N-glyoxylyl peptide CHOCO-Pro-Ile-Val-NH2, which fulfills the specificity 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 interactions were visualized between its hydrated form and the catalytic aspartates using molecular modeling. Increasing the length of the peptide sequence led to compounds acting only as substrates.
Qasmi
D
D
Institut de Chimie des Substances Naturelles-CNRS, Gif-sur-Yvette, France.
de Rosny
E
E
René
L
L
Badet
B
B
Vergely
I
I
Boggetto
N
N
Reboud-Ravaux
M
M
D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001224:Aspartic Acid / Q000737:chemistry / Q000378:metabolism; D001667:Binding, Competitive; D002384:Catalysis; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D006038:Glyoxylates / Q000737:chemistry* / Q000378:metabolism; D016333:HIV Protease / Q000737:chemistry*; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry; D013329:Structure-Activity Relationship
D000596:Amino Acids; D019380:Anti-HIV Agents; D006038:Glyoxylates; D017320:HIV Protease Inhibitors; D011994:Recombinant Proteins; D001224:Aspartic Acid; D016333:HIV Protease