title: Borano-nucleotides: new analogues to circumvent HIV-1 RT-mediated nucleoside drug-resistance.
abstract: 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.
authors.affiliation: CNRS, UMR 6098, Architecture et Fonction des Macromolecules Biologiques, Marseille Cedex 9, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Alvarez
authors.forename: Jérôme
authors.initials: J
authors.lastname: Deval
authors.forename: Boulbaba
authors.initials: B
authors.lastname: Selmi
authors.forename: Karine
authors.initials: K
authors.lastname: Barral
authors.forename: Joelle
authors.initials: J
authors.lastname: Boretto
authors.forename: Catherine
authors.initials: C
authors.lastname: Guerreiro
authors.forename: Laurence
authors.initials: L
authors.lastname: Mulard
authors.forename: Robert
authors.initials: R
authors.lastname: Sarfati
authors.forename: Bruno
authors.initials: B
authors.lastname: Canard
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001895:Boron / Q000737:chemistry*; D001896:Boron Compounds / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D024882:Drug Resistance, Viral; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors; D007700:Kinetics; D009154:Mutation; D009690:Nucleic Acid Conformation; D010100:Oxygen / Q000737:chemistry; D010710:Phosphates / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000596:Amino Acids; D019380:Anti-HIV Agents; D001896:Boron Compounds; D010710:Phosphates; D054303:HIV Reverse Transcriptase; D001895:Boron; D010100:Oxygen