Department of Chemistry, Georgia State University, Atlanta, Georgia.
Current Address: Biologics Drug Product Development and Delivery, Janssen Research and Development, Malvern, Pennsylvania.
Curr Protoc. 2023 Apr;3(4):e729. doi: 10.1002/cpz1.729.
Compounds that bind in the DNA minor groove have provided critical information on DNA molecular recognition, have found extensive uses in biotechnology, and are providing clinically useful drugs against diseases as diverse as cancer and sleeping sickness. This review focuses on the development of clinically useful heterocyclic diamidine minor groove binders. These compounds show that the classical model for minor groove binding in AT DNA sequences must be expanded in several ways: compounds with nonstandard shapes can bind strongly to the groove, water can be directly incorporated into the minor groove complex in an interfacial interaction, compounds can be designed to recognize GC and mixed AT/GC base pair sequences, and stacked dimers can form to recognize specific sequences. © 2023 Wiley Periodicals LLC.
与 DNA 小沟结合的化合物为 DNA 分子识别提供了关键信息，在生物技术中得到了广泛应用，并为癌症和昏睡病等各种疾病提供了临床有用的药物。这篇综述重点介绍了临床有用的杂环二脒类小分子沟结合剂的发展。这些化合物表明，经典的 AT DNA 序列中小沟结合模型必须在几个方面扩展：具有非标准形状的化合物可以强烈结合到沟中，水可以在界面相互作用中直接掺入到小沟复合物中，化合物可以设计来识别 GC 和混合 AT/GC 碱基对序列，并且堆叠的二聚体可以形成以识别特定序列。© 2023 年 Wiley 期刊 LLC。
