Gln151 of HIV-1 reverse transcriptase acts as a steric gate towards clinically relevant acyclic phosphonate nucleotide analogues.

Antoine Frangeul , Cécile Bussetta , Jérôme Deval , Karine Barral (1) , Karine Alvarez (2) , Bruno Canard (2)

1 CRCM - Centre de Recherche en Cancérologie de Marseille
2 AFMB - Architecture et fonction des macromolécules biologiques

In the treatment of HIV, the loose active site of the HIV-1 reverse transcriptase (RT) allows numerous nucleotide analogues to act as proviral DNA 'chain-terminators'. Acyclic nucleotide phosphonate analogues (ANPs) represent a particular class of nucleotide analogue that does not possess a ribose moiety. The structural basis for their substrate efficiency regarding viral DNA polymerases is poorly understood.

Domains: Chemical Sciences; Chemical Sciences; Medicinal Chemistry

Antoine Frangeul, Cécile Bussetta, Jérôme Deval, Karine Barral, Karine Alvarez, et al.. Gln151 of HIV-1 reverse transcriptase acts as a steric gate towards clinically relevant acyclic phosphonate nucleotide analogues.. Antiviral Therapy, 2019, 13 (1), pp.115-24. ⟨hal-02061712⟩