Title: Interactions of the dimeric triad of HIV-1 aspartyl protease with inhibitors
Authors: Mager, Peter P ×
De Clercq, Erik
Froeyen, Mathy
Reinhardt, Robert #
Issue Date: Jan-2003
Publisher: Harwood Academic Publishers
Series Title: Drug Design and Discovery vol:18 issue:2-3 pages:53-64
Abstract: Strong hydrogen-bonding forces between the Thr26 and Thr26' of the protease stabilize the internal cage of the dimeric triad of the aspartyl HIV-1 protease (Asp25Thr26Gly27 and Asp25' Thr26'Gly27', respectively). The interaction of reversible inhibitors of HIV-1 protease is based on (i) strong hydrogen-bonding forces between the main chain (--CONH--) oxygen atoms of Gly27 and/or Gly27' and hydrogen-bond donating moieties of a drug, and (ii) hydrogen bonds between the oxygen of the catalytic Asp25 and/or Asp25' carboxylates and aliphatic hydroxyl groups of a drug. The free entry of natural substrates into the active-site cavity is sterically hindered by inhibitors, so that the catalytic Asp carboxylates cannot interact with natural substrates. Irreversible inhibitors interact with the nucleophilic carboxylate moiety of Asp25 of HIV-1 protease by covalent bonding.
ISSN: 1055-9612
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
Medicinal Chemistry (Rega Institute)
× corresponding author
# (joint) last author

Files in This Item:

There are no files associated with this item.

Request a copy


All items in Lirias are protected by copyright, with all rights reserved.