Skip to main content
Go to the home page of the European Commission (opens in new window)
English English
CORDIS - EU research results
CORDIS
Content archived on 2024-04-30

Rational Design, Synthesis & Evaluation of New Protease Inhibitors agains AIDS

Objective

The network will develop mechanism-based and dissociative inhibitors of HIV-1 protease. In vitro evaluation will be performed on the pure HIV protease produced within the network. The anti-HIV activities and the toxicity of synthetic compounds will be simultaneously evaluated on different cell lines. Finally, the in vivo activity of selected inhibitors will be tested on macaques.

The project is concerned with the identification of new molecules which act upon AIDS virus protease, but whose mechanism would be different from other known anti-proteases. This Concerted Action takes advantage of the participants' expertise in molecular modelling, organic synthesis, protein expression and purification, enzyme kinetics peptide vectorization and in vivo tests.
The known X-ray structures of the protease inhibitor complexes will first be used to characterise the pharmacophore and design new active-site inhibitors on the one hand and dissociative inhibitors on the other hand. Mechanism-based inhibitors (suicide substrates) would act in the active-site causing an irreversible inhibition of enzymatic activity whereas dissociative inhibitors will act in inhibiting dimerization. or promoting dissociation of protease into monomers. Combinatorial libraries will be used complementary to computer aided design. The synthesis of suicide substrates relies upon the development of synthetic routes to alpha-substituted glycines whereas dissociative inhibitors require synthesis of peptides and peptidomimetics.
Compounds synthesised will be evaluated in vitro using recombinant protease produced within the network and kinetically characterised. The anti-HIV activity will be simultaneously evaluated using replicating virus in different cell lines. The determination of in vivo efficacy using macaque infected with the engineered simian virus will be restricted to the most active compounds.

Fields of science (EuroSciVoc)

CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.

You need to log in or register to use this function

Call for proposal

Data not available

Coordinator

Centre National de la Recherche Scientifique
EU contribution
No data
Address
AVENUE DE LA TERRASSE
91198 GIF-SUR-YVETTE
France

See on map

Total cost
No data