Profiling sirtuin activity using Copper-free click chemistry.
Profiling sirtuin activity using Copper-free click chemistry.
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DOI：
10.1016/j.bioorg.2021.105413
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发表时间：
2021-12
影响因子：
5.1
通讯作者：
Cen Y
中科院分区：
文献类型：
--
作者：
Curry AM;Cohen I;Zheng S;Wohlfahrt J;White DS;Donu D;Cen Y
哺乳动物去乙酰化酶是一组翻译后修饰酶，它们以 NAD+ 依赖性方式去除赖氨酸残基上的酰基修饰。尽管最初被提议为组蛋白脱乙酰酶 (HDAC)，但现在已知它们也能靶向其他细胞酶和蛋白质。 Sirtuin 催化的简单酰胺水解具有深远的生物学后果，包括抑制基因表达、促进 DNA 损伤修复以及调节葡萄糖和脂质代谢。人类sirtuins作为治疗癌症和神经退行性疾病等疾病的潜在治疗靶点一直受到学术界和工业界的广泛关注。为了更好地了解它们在各种细胞事件中的作用，创新的化学探针受到高度追捧。目前的研究重点是开发基于活性的化学探针 (ABP)，用于分析生物样品中的 Sirtuin 活性。合成了含环辛炔和含叠氮基的探针，以实现随后与荧光团或生物素的无铜“点击”缀合。两组结构相关的 ABP 表现出不同的标记效率和选择性：含有环辛炔的探针未能将重组沉默调节蛋白标记到任何可感知的水平，而含有叠氮基的 ABP 则显示出良好的亚型选择性。进一步分析了含叠氮基的 ABP 标记蛋白质混合物和细胞裂解物中单个去乙酰化酶亚型的能力。这些生物相容性 ABP 使动态细胞蛋白质活性变化的研究成为可能。
The mammalian sirtuins are a group of posttranslational modification enzymes that remove acyl modifications from lysine residues in an NAD+-dependent manner. Although initially proposed as histone deacetylases (HDACs), they are now known to target other cellular enzymes and proteins as well. Sirtuin-catalyzed simple amide hydrolysis has profound biological consequences including suppression of gene expression, promotion of DNA damage repair, and regulation of glucose and lipid metabolism. Human sirtuins have been intensively pursued by both academia and industry as potential therapeutic targets for the treatment of diseases such as cancer and neurodegeneration. To gain a better understanding of their roles in various cellular events, innovative chemical probes are highly sought after. This current study focuses on the development of activity-based chemical probes (ABPs) for the profiling of sirtuin activity in biological samples. Cyclooctyne-containing and azido-containing probes were synthesized to enable the subsequent copper-free “click” conjugation to either a fluorophore or biotin. The two groups of structurally related ABPs demonstrated different labeling efficiency and selectivity: the cyclooctyne-containing probes failed to label recombinant sirtuins to any appreciable level, while the azido-containing ABPs showed good isoform selectivity. The azido-containing ABPs were further analyzed for their ability to label an individual sirtuin isoform in protein mixtures and cell lysates. These biocompatible ABPs allow the study of dynamic cellular protein activity change to become possible.
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影响因子：
46.2
作者：
Jewett JC;Bertozzi CR
通讯作者：
Bertozzi CR
DOI：
10.3390/molecules26010011
发表时间：
2020-12-22
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Curry AM;Barton E;Kang W;Mongeluzi DV;Cen Y
通讯作者：
Cen Y
DOI：
10.1006/bbrc.2000.3000
发表时间：
2000-07-05
影响因子：
3.1
作者：
Frye, RA
通讯作者：
Frye, RA
DOI：
10.1146/annurev.pathol.4.110807.092250
发表时间：
2010
期刊：
Annual review of pathology
影响因子：
--
作者：
Haigis MC;Sinclair DA
通讯作者：
Sinclair DA
影响因子：
8
作者：
Abril YLN;Fernandez IR;Hong JY;Chiang YL;Kutateladze DA;Zhao Q;Yang M;Hu J;Sadhukhan S;Li B;He B;Remick B;Bai JJ;Mullmann J;Wang F;Maymi V;Dhawan R;Auwerx J;Southard T;Cerione RA;Lin H;Weiss RS
通讯作者：
Weiss RS