Objective
HIV-1 develops multidrug resistance in patients receiving various combination chemotherapies. To identify analogues active against HIV-1 drug-resistant strains, we plan to synthesize and investigate the structure, conformation and selected physico-chemical and biological properties of a range of new and known substituted with lipophilic groups, at 2, 4 and 3' positions 2',3'-dideoxynucleoside analogues. Compounds of this type should act as competitive drug-resistant reverse transcriptase (RT-Res) inhibitors.
Other compounds to be synthesized and examined are new and known nucleosides from the group of 4'-C-substituted 2',3'-dideoxy-3'-fluoronucleosides. Slowly releasing forms of these compounds will be also prepared. Drug-resistant reverse transcriptases will be obtained from engineered HIV-1 drug-resistant mutants, as well as by recombinant techniques. Interactions of synthesized compounds with the wild type HIV-1 RT, as well as with HIV-1-Res RT, will be investigated.
Fields of science
Call for proposal
FP6-2005-LIFESCIHEALTH-7
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