title: Peptide aldehydes as inhibitors of HIV protease.
abstract: We have recently shown that alpha-MAPI, a peptidic aldehyde of microbial origin, inhibits the HIV protease with a potency comparable to pepstatin, having, differently from pepstatin, no activity on other aspartic proteases. In this study different peptide derivatives containing a C-terminal aldehyde have been tested to assess the potential of this function for the inhibition of HIV protease. The results of our analysis correspond with the recently published subsite preferences of the viral enzyme, indicating that aldehydes bind to the active site of the HIV protease. Our data suggest that peptide aldehydes can act in their hydrated forms as transition state analogues with the most potent inhibitor having an IC50 of 0.9 microM.
authors.affiliation: Lepetit Research Center, MMDRI, Gerenzano, VA, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Sarubbi
authors.forename: P F
authors.initials: PF
authors.lastname: Seneci
authors.forename: M R
authors.initials: MR
authors.lastname: Angelastro
authors.forename: N P
authors.initials: NP
authors.lastname: Peet
authors.forename: M
authors.initials: M
authors.lastname: Denaro
authors.forename: K
authors.initials: K
authors.lastname: Islam
mesh_terms: D000447:Aldehydes / Q000737:chemistry / Q000494:pharmacology*; D000595:Amino Acid Sequence; D002154:Calpain / Q000037:antagonists & inhibitors; D016333:HIV Protease / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000737:chemistry*; D015497:HIV-1 / Q000201:enzymology*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000447:Aldehydes; D017320:HIV Protease Inhibitors; D010455:Peptides; D002154:Calpain; D016333:HIV Protease