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Sirtuins:多效的药物靶点。

Sirtuins: multifaceted drug targets.

机构信息

Aurigene Discovery Technologies Ltd, Electronic City, Bangalore 560100, India.

出版信息

Curr Mol Med. 2011 Dec;11(9):709-18. doi: 10.2174/156652411798062412.

Abstract

Sirtuin (Sir2) proteins being key regulators of numerous cellular processes have been, over the recent past, the subject of intense study. Sirs have been implicated in diverse physiological processes ranging from aging and cancer to neurological dysfunctions. Studies on Sir2s using tools of genetics, molecular biology, biochemistry and structural biology have provided significant insight into the diverse functions of this class of deacetylases. This apart, medicinal chemistry approaches have enabled the discovery of modulators (both activators and inhibitors) of Sir2 activity of diverse chemical structures and properties. The availability of these small molecule modulators of Sir2 activity not only has pharmacological significance but also opens up the possibility of exploiting chemical genetic approaches in understanding the role of this multi-functional enzyme in cellular processes.

摘要

Sirtuin (Sir2) 蛋白是许多细胞过程的关键调节剂,在过去的一段时间里,它们一直是研究的热点。Sirs 与从衰老和癌症到神经功能障碍等各种生理过程有关。使用遗传学、分子生物学、生物化学和结构生物学工具对 Sir2s 的研究为这一类去乙酰化酶的多种功能提供了重要的见解。除此之外,药物化学方法还能够发现具有不同化学结构和性质的 Sir2 活性调节剂(激活剂和抑制剂)。这些 Sir2 活性小分子调节剂的出现不仅具有药理学意义,而且还为利用化学遗传方法来理解这种多功能酶在细胞过程中的作用提供了可能性。

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