Chaires J B
Department of Biochemistry, University of Mississippi Medical Center, Jackson 39216-4505, USA.
Curr Opin Struct Biol. 1998 Jun;8(3):314-20. doi: 10.1016/s0959-440x(98)80064-x.
Significant progress has been made over the past few years in studies of drug-DNA interactions. Structure-based design strategies have yielded new DNA-binding agents with clinical promise. The hairpin polyamides represent the result of a design strategy with outstanding potential. One specific molecule of this class has now been proven to inhibit the expression of a specific gene in vivo. A new bisintercalating anthracycline antibiotic binds with high affinity to DNA, and appears to overcome a specific form of multidrug resistance. Progress in fundamental studies of drug binding to DNA continues, with detailed thermodynamic studies providing new insights into the forces that drive complex formation. New tools have been developed in order to characterize both the binding mode and the sequence specificity of drug binding to DNA, tools that will enable the fundamental aspects of these biologically important reactions to be understood in more detail.
在过去几年中,药物与DNA相互作用的研究取得了重大进展。基于结构的设计策略已产生了具有临床应用前景的新型DNA结合剂。发夹型聚酰胺就是一种具有巨大潜力的设计策略的成果。现已证明该类中的一种特定分子可在体内抑制特定基因的表达。一种新型双插入蒽环类抗生素能以高亲和力与DNA结合,并且似乎能克服一种特定形式的多药耐药性。药物与DNA结合的基础研究仍在继续,详细的热力学研究为驱动复合物形成的作用力提供了新的见解。为了表征药物与DNA结合的模式和序列特异性,已开发出了新工具,这些工具将使人们能够更详细地了解这些生物学重要反应的基本方面。