School of Pharmacy, Jiangsu University, 301 Xuefu Road, Zhenjiang 212013, PR China.
Eur J Med Chem. 2013 Jan;59:132-40. doi: 10.1016/j.ejmech.2012.11.014. Epub 2012 Nov 20.
Silent information regulator 2 (Sir2) enzymes or sirtuins are a family of NAD(+)-dependent protein N(ε)-acetyl-lysine (AcK) deacetylases. Sirtuins are also evolutionarily conserved proteins that are present in all kingdoms of life ranging from bacteria to humans. Interestingly, it was recently found that the sirtuins found in various human parasites (especially the Plasmodium, Trypanosoma, and Leishmania species) were pro-survival for the parasites under various conditions. Therefore, these parasitic sirtuins have emerged as novel anti-parasitic therapeutic targets. This article reviews the currently available structural, biochemical, pharmacological, and medicinal chemistry studies on these enzymes, and discusses the perspectives of selectively targeting the parasitic sirtuins as a novel therapeutic strategy for the human parasitic diseases.
沉默信息调节因子 2 (Sir2) 酶或称为 sirtuins 是一类烟酰胺腺嘌呤二核苷酸 (NAD(+)) 依赖的蛋白 N(ε)-乙酰基-赖氨酸 (AcK) 去乙酰化酶。Sirtuins 也是进化上保守的蛋白,存在于从细菌到人类的所有生命领域。有趣的是,最近发现各种人类寄生虫(尤其是疟原虫、锥虫和利什曼原虫)中的 sirtuins 在各种条件下对寄生虫的生存都是至关重要的。因此,这些寄生的 sirtuins 已成为新的抗寄生虫治疗靶点。本文综述了目前关于这些酶的结构、生化、药理学和药物化学研究,并讨论了选择性针对寄生 sirtuins 作为一种新的人类寄生虫病治疗策略的前景。