Peptide aldehydes as inhibitors of HIV protease

FEBS Letters

Peet, Norton P.¹  Sarubbi, Edoardo²  Denaro, Maurizio²  Angelastro, Michael R.¹  Seneci, Pier Fausto²  Islam, Khalid² 

[1] Marion Merrell Dow Research Institute, Cincinnati, OH, USA;Lepetit Research Center, MMDRI, Gerenzano, VA, Italy

关键词: Human immunodeficiency virus;    Aspartic protease;    Microbial alkaline protease inhibitor;    Peptide aldehyde;    Transition state analogue;    HIV;    human immunodeficiency virus;    AIDS;    acquired immunodeficiency syndrome;    MAPI;    microbial alkaline protease inhibitor;    CI;    calpain inhibitor;    Cbz;    carbobenzoxy;    Sta;    statine = 3-hydroxy-4-amino-6-methyl-heptanoic acid;    Cpd;    capreomycidine = α-(2-iminohexahydro-4-pyrimidyl)glycine;   

DOI  :  10.1016/0014-5793(93)80557-B

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

We have recently shown that α-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 μM.

【 授权许可】

Unknown