Qi Yun-Kun, Ai Hua-Song, Li Yi-Ming, Yan Baihui
Department of Anesthesiology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Department of Medicinal Chemistry, School of Pharmacy, Qingdao University, Qingdao, China.
Front Chem. 2018 Feb 6;6:19. doi: 10.3389/fchem.2018.00019. eCollection 2018.
In the post-genome era, epigenetics has received increasing attentions in recent years. The post-translational modifications (PTMs) of four core histones play central roles in epigenetic regulation of eukaryotic genome by either directly altering the biophysical properties of nucleosomes or by recruiting other effector proteins. In order to study the biological functions and structural mechanisms of these histone PTMs, an obligatory step is to prepare a sufficient amount of homogeneously modified histones. This task cannot be fully accomplished either by recombinant technology or enzymatic modification. In this context, synthetic chemists have developed novel protein synthetic tools and state-of-the-art chemical ligation strategies for the preparation of homologous modified histones. In this review, we summarize the recent advances in the preparation of modified histones, focusing on the total chemical synthesis strategies. The importance and potential of synthetic chemistry for the study of histone code will be also discussed.
在后基因组时代，表观遗传学近年来受到越来越多的关注。四种核心组蛋白的翻译后修饰（PTMs）通过直接改变核小体的生物物理特性或招募其他效应蛋白，在真核基因组的表观遗传调控中发挥核心作用。为了研究这些组蛋白PTMs的生物学功能和结构机制，一个必不可少的步骤是制备足够量的均匀修饰组蛋白。无论是重组技术还是酶促修饰都无法完全完成这项任务。在此背景下，合成化学家开发了新型蛋白质合成工具和最先进的化学连接策略来制备同源修饰组蛋白。在本综述中，我们总结了修饰组蛋白制备方面的最新进展，重点关注全化学合成策略。还将讨论合成化学在组蛋白密码研究中的重要性和潜力。
