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Peptide aldehydes as inhibitors of HIV protease
Author(s) -
Sarubbi Edoardo,
Seneci Pier Fausto,
Angelastro Michael R.,
Peet Norton P.,
Denaro Maurizio,
Islam Khalid
Publication year - 1993
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(93)80557-b
Subject(s) - pepstatin , protease , proteases , chemistry , peptide , biochemistry , enzyme , hiv 1 protease , protease inhibitor (pharmacology) , enzyme inhibitor , saquinavir , aldehyde , stereochemistry , human immunodeficiency virus (hiv) , biology , virology , antiretroviral therapy , viral load , catalysis
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 IC 50 of 0.9 μM.