Borano-nucleotides: new analogues to circumvent HIV-1 RT-mediated nucleoside drug-resistance.
Alvarez K, Deval J, Selmi B, Barral K, Boretto J, Guerreiro C, Mulard L, Sarfati R, Canard B
Alpha-boranophosphates suppress RT-mediated resistance when the catalytic rate of incorporation (kpol) of the analogue 5′-triphosphate is responsable for drug resistance, such as in the case of K65R mutant and ddNTPs, and Q151M toward AZTTP and ddNTPs. This suppression is also observed with BH3-d4T and BH3-3TC toward their clinically relevant mutants Q151M and M184V. Moreover, the presence of the borano (BH3-) group renders the incorporation of the analogue independent from amino-acid substitutions in RT. To our knowledge, this is the first example of rescue of polymerase activity by means of a nucleotide analogue.Lire l‘article