Department of Physics, University of Alberta, Edmonton, AB, Canada.
Drug Discov Today. 2012 Aug;17(15-16):913-20. doi: 10.1016/j.drudis.2012.04.008. Epub 2012 Apr 25.
Base excision repair (BER) is the fundamental pathway responsible for the elimination of damaged DNA bases and repair of DNA single-strand breaks generated spontaneously or produced by DNA-damaging agents. Among the essential enzymes that are required to achieve the BER reaction is DNA polymerase beta (pol β), which has been regarded as a potential therapeutic target. More than 60 pol β-inhibitors have been identified so far; however, most of them are either not potent or not specific enough to become a drug. In this article we compile an essential knowledge base regarding the structures, the modes of inhibition and the activities of these pharmacologically interesting molecules.
碱基切除修复 (BER) 是负责消除受损 DNA 碱基并修复自发产生或由 DNA 损伤剂产生的 DNA 单链断裂的基本途径。在实现 BER 反应所需的必需酶中，有一种酶是 DNA 聚合酶 β (pol β)，它一直被视为一个潜在的治疗靶点。到目前为止，已经鉴定出超过 60 种 pol β 抑制剂；然而，其中大多数要么不够有效，要么不够特异，无法成为药物。在本文中，我们编译了一个关于这些具有药理活性的分子的结构、抑制模式和活性的基本知识库。
