Wright G E, Brown N C
Department of Pharmacology, University of Massachusetts Medical School, Worcester 01655.
Pharmacol Ther. 1990;47(3):447-97. doi: 10.1016/0163-7258(90)90066-b.
Inhibitory and substrate properties of analogs of deoxyribonucleoside triphosphates toward DNA polymerases are reviewed. A general introduction is followed by a description of DNA polymerases and the reaction that they catalyze, and sites at which substrate analogs may inhibit them. Effects of modifications in the major family of compounds, nucleotide derivatives, at the base, sugar and triphosphate portions of the molecule, are summarized with respect to retention of substrate properties and generation of inhibitory properties. Structure-activity relationships and the basis of selectivity in the second family of compounds, deoxyribonucleotide mimics, are also presented. Conclusions are drawn regarding the structural basis of inhibitor selectivity and mechanism, relationship between in vitro and in vivo effects of inhibitors, and the promise of inhibitors as probes for study of active sites of DNA polymerases.
本文综述了脱氧核糖核苷三磷酸类似物对DNA聚合酶的抑制特性和底物特性。在进行总体介绍之后，描述了DNA聚合酶及其催化的反应，以及底物类似物可能抑制它们的位点。总结了在化合物主要家族（核苷酸衍生物）的碱基、糖和三磷酸部分进行修饰时，对保留底物特性和产生抑制特性的影响。还介绍了第二类化合物（脱氧核苷酸模拟物）的构效关系和选择性基础。得出了关于抑制剂选择性和作用机制的结构基础、抑制剂体外和体内效应之间的关系，以及抑制剂作为研究DNA聚合酶活性位点探针的前景的结论。
