Maji Basudeb, Bhattacharya Santanu
Department of Organic Chemistry, Indian Institute of Science, Bangalore-560012, India.
Chem Commun (Camb). 2014 Jun 21;50(49):6422-38. doi: 10.1039/c4cc00611a. Epub 2014 Apr 3.
Telomerases are an attractive drug target to develop new generation drugs against cancer. A telomere appears from the chromosomal termini and protects it from double-stranded DNA degradation. A short telomere promotes genomic instability, like end-to-end fusion and regulates the over-expression of the telomere repairing enzyme, telomerase. The telomerase maintains the telomere length, which may lead to genetically abnormal situations, leading to cancer. Thus, the design and synthesis of an efficient telomerase inhibitor is a viable strategy toward anticancer drugs development. Accordingly, small molecule induced stabilization of the G-quadruplex structure, formed by the human telomeric DNA, is an area of contemporary scientific art. Several such compounds efficiently stabilize the G-quadruplex forms of nucleic acids, which often leads to telomerase inhibition. This Feature article presents the discovery and development of the telomere structure, function and evolution in telomere targeted anticancer drug design and incorporates the recent advances in this area, in addition to discussing the advantages and disadvantages in the methods, and prospects for the future.
端粒酶是开发新一代抗癌药物的一个有吸引力的药物靶点。端粒出现在染色体末端，保护其免受双链DNA降解。短端粒会促进基因组不稳定，如端对端融合，并调节端粒修复酶端粒酶的过度表达。端粒酶维持端粒长度，这可能导致基因异常情况，进而引发癌症。因此，设计和合成高效的端粒酶抑制剂是抗癌药物开发的可行策略。相应地，小分子诱导人端粒DNA形成的G-四链体结构的稳定化是当代科学技术的一个领域。几种这样的化合物能有效地稳定核酸的G-四链体形式，这通常会导致端粒酶抑制。这篇专题文章介绍了端粒靶向抗癌药物设计中端粒的结构、功能和进化的发现与发展，除了讨论方法的优缺点和未来前景外，还纳入了该领域的最新进展。
