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Preparation and identification of new HIV reverse transcriptase inhibitors targeted against HIV strains resistant to anti-HIV/AIDS drugs

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.

Call for proposal

FP6-2005-LIFESCIHEALTH-7
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Coordinator

INSTYTUT BIOCHEMII I BIOFIZYKI POLSKIEJ AKADEMII NAUK
Address
Pawinskiego 5A
Warszawa
Poland

Participants (5)

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE
France
Address
Rue Michel Ange, 3
Paris
INPHENO AG
Switzerland
Address
Vesalgasse 1
Basel
INSTYTUT CHEMII BIOORGANICZNEJ POLSKIEJ AKADEMII NAUK
Poland
Address
Noskowskiego 12/14
Poznan
INSTYTUT MEDYCYNY DOSWIADCZALNEJ I KLINICZNEJ IM. M. MOSSAKOWSKIEGO POLSKIEJ AKADEMII NAUK
Poland
Address
Pawinskiego 5
Warszawa
INSTYTUT PRZEMYSLU ORGANICZNEGO ODDZIAL W PSZCZYNIE
Poland
Address
Doswiadczalna 27
Pszczyna