Gatto B, Capranico G, Palumbo M
Department of Pharmaceutical Sciences, University of Padova, Via Marzolo 5, Padova, 35131, Italy.
Curr Pharm Des. 1999 Mar;5(3):195-215.
DNA-topoisomerases, a family of DNA-processing enzymes, represent the pharmacological target of major clinically useful chemotherapeutic agents. These drugs essentially act by trapping a topoisomerase-DNA cleavable complex, an intermediate in the enzyme s catalytic cycle. Research activity in this field continues to grow exponentially, resulting in a wealth of new information on the functional role and the biochemical and structural properties of the enzymes. In addition, the drug pharmacophores have been further characterized, along with their sequence preferences, and key interactions with the target macromolecules are being unveiled. This review will discuss the recent advances in elucidating the mode of action of DNA-topoisomerases and of topoisomerase-targeted anticancer agents.
DNA拓扑异构酶是一类DNA处理酶，是临床上主要有用的化疗药物的药理学靶点。这些药物主要通过捕获拓扑异构酶-DNA可裂解复合物起作用，该复合物是酶催化循环中的一个中间体。该领域的研究活动继续呈指数级增长，产生了大量关于这些酶的功能作用、生化和结构特性的新信息。此外，药物药效基团及其序列偏好得到了进一步表征，与靶大分子的关键相互作用也正在被揭示。本综述将讨论在阐明DNA拓扑异构酶和拓扑异构酶靶向抗癌药物作用模式方面的最新进展。
