Department of Chemistry, Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, United Kingdom.
School of Chemical Sciences and National Institute for, Cellular Biotechnology and Nano Research Facility, Dublin City University, Glasnevin, Dublin, 9, Ireland.
Chembiochem. 2021 Jul 1;22(13):2184-2205. doi: 10.1002/cbic.202000838. Epub 2021 Apr 9.
DNA binding metal complexes are synonymous with anticancer drug discovery. Given the array of structural and chemical reactivity properties available through careful design, metal complexes have been directed to bind nucleic acid structures through covalent or noncovalent binding modes. Several recognition modes - including crosslinking, intercalation, and oxidation - are central to the clinical success of broad-spectrum anticancer metallodrugs. However, recent progress in nucleic acid click chemistry coupled with advancement in our understanding of metal complex-nucleic acid interactions has opened up new avenues in genetic engineering and targeted therapies. Several of these applications are enabled by the hybridisation of oligonucleotide or polyamine probes to discrete metal complexes, which facilitate site-specific reactivity at the nucleic acid interface under the guidance of the probe. This Review focuses on recent advancements in hybrid design and, by way of an introduction to this topic, we provide a detailed overview of nucleic acid structures and metal complex-nucleic acid interactions. Our aim is to provide readers with an insight on the rational design of metal complexes with DNA recognition properties and an understanding of how the sequence-specific targeting of these interactions can be achieved for gene engineering applications.
DNA 结合金属配合物是抗癌药物发现的同义词。考虑到通过精心设计可以获得的一系列结构和化学反应性特性，金属配合物已被引导通过共价或非共价结合模式与核酸结构结合。几种识别模式——包括交联、嵌入和氧化——是广谱抗癌金属药物临床成功的核心。然而，核酸点击化学的最新进展以及我们对金属配合物-核酸相互作用的理解的进步，为基因工程和靶向治疗开辟了新途径。这些应用中的几种是通过将寡核苷酸或多胺探针杂交到离散的金属配合物来实现的，这在探针的指导下促进了核酸界面处的特异性反应。本综述重点介绍了混合设计的最新进展，并通过介绍该主题，我们提供了核酸结构和金属配合物-核酸相互作用的详细概述。我们的目的是为读者提供具有 DNA 识别特性的金属配合物的合理设计的见解，并了解如何针对这些相互作用实现序列特异性靶向，以用于基因工程应用。
