Borano-nucleotides: new analogues to circumvent HIV-1 RT-mediated nucleoside drug-resistance

Nucleosides Nucleotides Nucleic Acids. 2005;24(5-7):419-21. doi: 10.1081/NCN-200059951.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / chemistry
  • Anti-HIV Agents / chemical synthesis*
  • Anti-HIV Agents / pharmacology
  • Boron / chemistry*
  • Boron Compounds / pharmacology*
  • Chemistry, Pharmaceutical / methods
  • Drug Design
  • Drug Resistance, Viral*
  • HIV Reverse Transcriptase / antagonists & inhibitors
  • Kinetics
  • Mutation
  • Nucleic Acid Conformation
  • Oxygen / chemistry
  • Phosphates / chemistry
  • Phosphates / pharmacology

Substances

  • Amino Acids
  • Anti-HIV Agents
  • Boron Compounds
  • Phosphates
  • HIV Reverse Transcriptase
  • Boron
  • Oxygen