Synthesis and primary evaluation of novel HIV-1 inhibitors.
The overcoming of antiviral drug resistance is an important challenge in the treatment of HIV-1 infection. According to the theory of viral error catastrophe, slightly increasing the mutation rate could exceed the error threshold for viability of a viral population and kill it. Investigation of this mechanism could lead to the discovery of new antiviral agents capable of bypassing viral resistance. To this aim, we designed several modified nucleosides. We describe here the synthesis and partial evaluation of 8-amido-2'-deoxyadenosine. The supplementary amide group on the base should allow base-pairing with several natural nucleosides, thus creating supplementary mutations that would kill the virus.
Architecture et Réactivité de l'ARN, UPR 9002 du CNRS, IBMC, Strasbourg, France.
Yazan
Y
El Safadi
Roland
R
Marquet
Anne-Marie
AM
Aubertin
Valérie
V
Vivet-Boudou
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D003839:Deoxyadenosines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D024882:Drug Resistance, Viral / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D008826:Microbial Sensitivity Tests; D014779:Virus Replication / Q000187:drug effects
D019380:Anti-HIV Agents; D003839:Deoxyadenosines