蛋白去乙酰化是生物体内一种重要的蛋白质修饰，它需要赖氨酸去乙酰化酶催化完成。Sirtuins是一类NAD+依赖型的赖氨酸去乙酰化酶，在基因转录、脂肪酸代谢、胰岛素分泌、细胞凋亡等许多生命过程中发挥重要作用。目前，确证sirtuins的生物学功能是该领域的一个研究热点，特别是对于它们所调控的信号通路以及与疾病的相关性还有待深入研究。以sirtuins为靶标，设计合成小分子探针，实现实时、原位定量调控sirtuins酶活，可极大促进体内sirtuins的生物学功能研究。为此，本课题将发展具有亚型选择性的sirtuins激动剂、抑制剂，这些激动剂、抑制剂能特异性地调节不同sirtuins亚型的酶活，作为探针分子，可用来帮助研究sirtuins的生物学功能。另外，因sirtuins在癌症、炎症、代谢性疾病和神经退行性疾病的发生、发展过程中扮演重要角色，这些探针化合物也可用于相关疾病的研究。

Protein deacetylation is an important post-translational protein modification, which is catalyzed by the lysine deacetylases (KDAC). Sirtuins, a class of NAD(+)-dependent KDAC, play important roles in many biological processes such as gene transcription, fatty acid metabolism, insulin secretion and apoptosis. Currently, many studies are focused on their functions, the signal pathways and their correlation to human diseases. To help study the biological functions of sirtuins, here we aim to develop isoform-selective sirtuins activators or inhibitors, which can serve as chemical probes to modulate the activity of various sirtuins in real-time and in situ. Moreover, sirtuins are involved in the genesis and development of cancer, inflammation, metabolic diseases and neurodegenerative diseases. Thus, these modulators may also be used in the study of the relevant diseases.