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

被引：9
|
作者：
Alvarez, K
Deval, J
Selmi, B
Barral, K
Boretto, J
Guerreiro, C
Mulard, L
Sarfati, R
Canard, B
机构：
[1] CNRS, UMR 6098, ESIL, F-13288 Marseille, France
[2] Inst Pasteur, Unite Chim Organ, Paris 15, France
来源：
NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS | 2005年 / 24卷 / 5-7期
关键词：
D O I：
10.1081/NCN-200059951
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
alpha-Boranophosphates suppress RT-mediated resistance when the catalytic rate of incorporation (k(pol))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 BH(3)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.
引用
收藏
页码：419 / 421
页数：3
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