KQTAR(TSuK)STGGKA | 1354905-74-0

• 分子结构分类: 有机化合物 - 有机聚合物 - 多肽
• 英文名称: KQTAR(TSuK)STGGKA
• 英文别名: H3K9TSu；4-[[(5S)-6-[[(2S)-1-[[(2S,3R)-1-[[2-[[2-[[(2S)-6-amino-1-[[(1S)-1-carboxyethyl]amino]-1-oxohexan-2-yl]amino]-2-oxoethyl]amino]-2-oxoethyl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-5-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-5-amino-2-[[(2S)-2,6-diaminohexanoyl]amino]-5-oxopentanoyl]amino]-3-hydroxybutanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-6-oxohexyl]amino]-4-sulfanylidenebutanoic acid
• CAS: 1354905-74-0
• 化学式: C₅₄H₉₇N₁₉O₁₉S
• 分子量: 1348.55
• InChiKey: YXKGYVHVWCCQGQ-DDGZQKRDSA-N

物化性质

• 密度：
  1.51±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -13.9
• 重原子数：
  93
• 可旋转键数：
  49
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  685
• 氢给体数：
  23
• 氢受体数：
  24

反应信息

• 作为反应物：
  描述：

  KQTAR(TSuK)STGGKA 、 NADH 在 human Sirt₅ 、 Cleland's reagent 作用下， 反应 0.08h， 生成 、 L-lysyl-L-glutaminyl-L-threonyl-L-alanyl-L-arginyl-L-lysyl-L-seryl-L-threonylglycylglycyl-L-lysyl-L-alanine 、 烟酰胺
  参考文献：
  名称：

  Thiosuccinyl Peptides as Sirt5-Specific Inhibitors

  摘要：

  Sirtuins, a class of enzymes known as nicotinamide adenine dinucleotide-dependent deacetylases, have been shown to regulate a variety of biological processes, including aging, transcription, and metabolism. Sirtuins are considered promising targets for treating several human diseases. There are seven sirtuins in humans (Sirt1-7). Small molecules that can target a particular human sirtuin are important for drug development and fundamental studies of sirtuin biology. Here we demonstrate that thiosuccinyl peptides are potent and selective Sirt5 inhibitors. The design of these inhibitors is based on our recent discovery that Sirt5 prefers to catalyze the hydrolysis of malonyl and succinyl groups, rather than an acetyl group, from lysine residues. Furthermore, among the seven human sirtuins, Sirt5 is the only one that has this unique acyl group preference. This study demonstrates that the different acyl group preferences of different sirtuins can be conveniently utilized to develop small molecules that selectively target different sirtuins.

  DOI：

  10.1021/ja2090417