蛋白质的翻译后修饰研究是后基因组时代的热点和前沿研究课题。而研究蛋白修饰的调控蛋白又是该领域的重要研究方向。探索蛋白质翻译后修饰的动态相互作用机制不仅可以深入认识蛋白质功能、调节机制及其生理、病理效应；同时，也为药物靶点的发现和靶向药物治疗奠定理论基础。近几年来，一些新的蛋白赖氨酸翻译后修饰相继被发现。特别是琥珀酰化及肉豆蔻酰化这两个独特的修饰，在生命体中很可能会具有某种特殊的生理或病理调节功能。去琥珀酰化及去肉豆蔻酰化的调控蛋白SIRT5和SIRT6已分别被发现，因此，针对这两种修饰的转移酶和Bromodomain的发现就成了亟待要解决的问题。本项目立足于最新和最前沿的研究成果，通过化学生物学的方法，设计合成新型分子探针,力图找到琥珀酰化及肉豆蔻酰化的调控蛋白-琥珀酰化/肉豆蔻酰化转移酶和Bromodomain。这将为进一步对这两种新修饰的调控机理研究和后续的药物靶点发现打下基础。

The study of protein posttranslational modification (PTM) is a hot and frontier research topic of the post-genomic era. Regulation of PTM is an important research direction in this field. Exploring protein post-translational modification of the dynamic interaction mechanism can not only be fully understood of protein function, regulatory mechanism, its physiological and pathological effects; but also to lay the theoretical foundation for the discovery of novel drug targets and drug targeted therapy. In recent several years, a number of new protein lysine post-translational modifications were found. Especially for succinylation and myristoylation, it must have some particular regulation of physiological or pathological function. SIRT5 and SIRT6 have already been found to be desuccinylase and demyristoylase, respectively.Therefore,succinyl/myristoyltransferase and their Bromodomain need to be discovered for figuring out the whole picture of the regulation of succinylation and myristoylation. The project is based on the latest and most frontier research, by the method of chemical biology with synthetic molecular as probes; try to find the rest of succinylated and to myristoylation regulatory proteins - succinyl/myristoyltransferase and their Bromodomain. The project also can lay the good foundation for follow-up study of regulatory mechanism and the discovery of novel drug targets.