Zhang Sulin, Wu Yanling, Zhang Wen
Lab of Chemical Biology & Molecular Drug Design, College of Pharmaceutical Science, Zhejiang University of Technology, 18 Chaowang Rd, Hangzhou, 310014 (China).
ChemMedChem. 2014 May;9(5):899-911. doi: 10.1002/cmdc.201300566. Epub 2014 Apr 11.
G-Quadruplexes are distinct nucleic acid secondary structures that are formed from G-rich DNA and RNA sequences; they are built around successive G-tetrads of Hoogsteen hydrogen-bonded guanine bases. The existence of G-quadruplex structures has been confirmed in the human telomere and genome, and their biological functions have been demonstrated. Thus, the prospect of using G-quadruplex structures as a novel target for drug design is important. This review focuses on structural polymorphism of G-quadruplexes on the basis of the classification of the strand number of the G-quadruplex formed and its interaction diversity with small molecules (G4-ligands) that display high affinity and, more importantly, selectivity. Also, we outlook some future challenges for G-quadruplex structure and ligand studies. Such information, together with the biological functions of for G-quadruplex, will be of crucial importance for the research and development of drugs that target G-quadruplexes formed from particular genes and human telomeres.
G-四链体是由富含鸟嘌呤的DNA和RNA序列形成的独特核酸二级结构；它们围绕着由Hoogsteen氢键连接的鸟嘌呤碱基的连续G-四联体构建而成。G-四链体结构在人类端粒和基因组中的存在已得到证实，其生物学功能也已得到证明。因此，将G-四链体结构用作药物设计新靶点具有重要意义。本综述基于所形成的G-四链体链数的分类及其与具有高亲和力且更重要的是具有选择性的小分子（G4配体）的相互作用多样性，重点关注G-四链体的结构多态性。此外，我们展望了G-四链体结构和配体研究未来面临的一些挑战。这些信息，连同G-四链体的生物学功能，对于靶向由特定基因和人类端粒形成的G-四链体的药物研发至关重要。
