DNA的非共价结合：抗癌药物的靶点

Title:Noncovalent Binding to DNA: Still a Target in Developing Anticancer Agents

Volume: 23 Issue: 36

Author(s): José Portugal and Francisca Barceló

Affiliation:

关键词: 抗肿瘤化疗，DNA结合药物，DNA识别，药物发现，作用机制，序列特异性

摘要: DNA-binding compounds are of extraordinary importance in medicine, accounting for a substantial portion of antitumor drugs in clinical usage. However, their mechanisms of action remain sometimes incompletely understood. This review critically examines two broad classes of molecules that bind noncovalently to DNA: intercalators and groove binders. Intercalators bind to DNA by inserting their chromophore moiety between two consecutive base pairs, whereas groove binders fit into the grooves of DNA. Noncovalent DNAinteractive drugs can recognize certain supramolecular DNA structures such as the Gquadruplexes found in telomeres and in numerous gene promoters, and they can act as topoisomerase I and II poisons. We discuss how DNA-binding compounds affect transcription and compete with protein factors for binding to consensus binding sites in gene promoters both in vitro and in cultured cancer cells. Moreover, we comment on the design of molecules that can tightly and specifically bind to any desired target DNA, such as various hairpin polyamides which efficacy as chemotherapeutic agents is being evaluated. At present, genome-wide studies, which provide details of events that may influence both cancer progression and therapeutic outcome, are a common way used to analyze the effects of DNA-binding compounds. A conclusive feature that emerges from reviewing the information on DNA-binding compounds is that both natural sources and chemical approaches can be productively used to obtain drugs to manipulate gene expression in cancer cells.

Cite this article as:

José Portugal and Francisca Barceló , Noncovalent Binding to DNA: Still a Target in Developing Anticancer Agents, Current Medicinal Chemistry 2016; 23 (36) . https://dx.doi.org/10.2174/0929867323666160902153511