cyclo-D-Asp(Pro-D-Pro-Val)-OH

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: cyclo-D-Asp(Pro-D-Pro-Val)-OH
• 英文别名: N(1)Pro-D-Pro-Val-D-Asp(1)-OH；(3S,10R,13S,16R)-2,8,12,15-tetraoxo-13-propan-2-yl-1,7,11,14-tetrazatricyclo[14.3.0.03,7]nonadecane-10-carboxylic acid
• 化学式: C₁₉H₂₈N₄O₆
• 分子量: 408.455
• InChiKey: OGKUBZBPEVSZGC-CXTNEJHOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  29
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  136
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  cyclo-D-Asp(Pro-D-Pro-Val)-OH 在 盐酸羟胺 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.75h， 生成 (3S,10R,13S,16R)-N-[4-(hydroxyamino)-4-oxobutyl]-2,8,12,15-tetraoxo-13-propan-2-yl-1,7,11,14-tetrazatricyclo[14.3.0.03,7]nonadecane-10-carboxamide
  参考文献：
  名称：

  Design and Synthesis of Simplified Largazole Analogues as Isoform-Selective Human Lysine Deacetylase Inhibitors

  摘要：

  Selective inhibition of KDAC isoforms while maintaining potency remains a challenge. Using the largazole macrocyclic depsipeptide structure as a starting point for developing new KDACIs with increased selectivity, a combination of four different simplified largazole analogue (SLA) scaffolds with diverse zinc-binding groups (for a total of 60 compounds) were designed, synthesized, and evaluated against class I KDACs 1, 3, and 8, and class II KDAC6. Experimental evidence as well as molecular docking poses converged to establish the cyclic tetrapeptides (CTPs) as the primary determinant of both potency and selectivity by influencing the correct alignment of the zinc-binding group in the KDAC active site, providing a further basis for developing new KDACIs of higher isoform selectivity and potency.

  DOI：

  10.1021/acs.jmedchem.5b01632
• 作为产物：
  描述：

  L-缬氨酸叔丁酯盐酸盐 在 哌啶 、 N-甲基吗啉 、 palladium 10% on activated carbon 、 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 三氟乙酸 、 diphenylphosphorylazide 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 80.5h， 生成 cyclo-D-Asp(Pro-D-Pro-Val)-OH
  参考文献：
  名称：

  Design and Synthesis of Simplified Largazole Analogues as Isoform-Selective Human Lysine Deacetylase Inhibitors

  摘要：

  Selective inhibition of KDAC isoforms while maintaining potency remains a challenge. Using the largazole macrocyclic depsipeptide structure as a starting point for developing new KDACIs with increased selectivity, a combination of four different simplified largazole analogue (SLA) scaffolds with diverse zinc-binding groups (for a total of 60 compounds) were designed, synthesized, and evaluated against class I KDACs 1, 3, and 8, and class II KDAC6. Experimental evidence as well as molecular docking poses converged to establish the cyclic tetrapeptides (CTPs) as the primary determinant of both potency and selectivity by influencing the correct alignment of the zinc-binding group in the KDAC active site, providing a further basis for developing new KDACIs of higher isoform selectivity and potency.

  DOI：

  10.1021/acs.jmedchem.5b01632

文献信息

• Design and Synthesis of Simplified Largazole Analogues as Isoform-Selective Human Lysine Deacetylase Inhibitors
  作者：Damodara N. Reddy、Flavio Ballante、Timothy Chuang、Adele Pirolli、Biagina Marrocco、Garland R. Marshall

  DOI：10.1021/acs.jmedchem.5b01632

  日期：2016.2.25

  Selective inhibition of KDAC isoforms while maintaining potency remains a challenge. Using the largazole macrocyclic depsipeptide structure as a starting point for developing new KDACIs with increased selectivity, a combination of four different simplified largazole analogue (SLA) scaffolds with diverse zinc-binding groups (for a total of 60 compounds) were designed, synthesized, and evaluated against class I KDACs 1, 3, and 8, and class II KDAC6. Experimental evidence as well as molecular docking poses converged to establish the cyclic tetrapeptides (CTPs) as the primary determinant of both potency and selectivity by influencing the correct alignment of the zinc-binding group in the KDAC active site, providing a further basis for developing new KDACIs of higher isoform selectivity and potency.