Qiu Jun, Wang Mingxue, Zhang Yan, Zeng Ping, Ou Tian-Miao, Tan Jia-Heng, Huang Shi-Liang, An Lin-Kun, Wang Honggen, Gu Lian-Quan, Huang Zhi-Shu, Li Ding
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou University City, 132 Waihuan East Road, Guangzhou 510006, P. R. China.
Curr Top Med Chem. 2015;15(19):1971-87. doi: 10.2174/1568026615666150515150803.
G-quadruplexes are four-stranded DNA structures formed from G-rich sequences that are built around tetrads of hydrogen-bonded guanine bases. Accumulating studies have revealed that G-quadruplex structures are formed in vivo and play important roles in biological processes such as DNA replication, transcription, recombination, epigenetic regulation, meiosis, antigenic variation, and maintenance of telomeres stability. Mounting evidence indicates that a variety of proteins are capable of binding selectively and tightly to G-quadruplex and play essential roles in G-quadruplex-mediated regulation processes. Some of these proteins promote the formation or/and stabilization of G-quadruplex, while some other proteins act to unwind G-quadruplex preferentially. From a drug discovery perspective, many of these G-quadruplex binding proteins and/or their complexes with G-quadruplexes are potential drug targets. Here, we present a general summary of reported G-quadruplex binding proteins and their biological functions, with focus on those of medicinal research significance. We elaborated the possibility for some of these G-quadruplex binding proteins and their complexes with G-quadruplexes as potential drug targets.
G-四链体是由富含鸟嘌呤的序列形成的四链DNA结构，这些序列围绕着氢键连接的鸟嘌呤碱基的四联体构建而成。越来越多的研究表明，G-四链体结构在体内形成，并在DNA复制、转录、重组、表观遗传调控、减数分裂、抗原变异和端粒稳定性维持等生物过程中发挥重要作用。越来越多的证据表明，多种蛋白质能够选择性且紧密地结合到G-四链体上，并在G-四链体介导的调控过程中发挥重要作用。其中一些蛋白质促进G-四链体的形成或/和稳定，而其他一些蛋白质则优先作用于解开G-四链体。从药物发现的角度来看，许多这些G-四链体结合蛋白和/或它们与G-四链体的复合物都是潜在的药物靶点。在此，我们对已报道的G-四链体结合蛋白及其生物学功能进行了全面总结，重点关注那些具有医学研究意义的蛋白。我们阐述了其中一些G-四链体结合蛋白及其与G-四链体的复合物作为潜在药物靶点的可能性。
