Cbz-Ile-Glu(O-t-Bu)-Thr-NHNH2 | 646532-74-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: Cbz-Ile-Glu(O-t-Bu)-Thr-NHNH2
• 英文别名: Cbz-Ile-Glu(OtBu)-Thr-NHNH2；tert-butyl (4S)-5-[[(2S,3R)-1-hydrazinyl-3-hydroxy-1-oxobutan-2-yl]amino]-4-[[(2S,3S)-3-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]amino]-5-oxopentanoate
• CAS: 646532-74-3
• 化学式: C₂₇H₄₃N₅O₈
• 分子量: 565.667
• InChiKey: OOMGDKCUUQUWHK-KOLYYURTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  40
• 可旋转键数：
  17
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  198
• 氢给体数：
  6
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  Cbz-Ile-Glu(O-t-Bu)-Thr-NHNH2 在 N-甲基吗啉 、 氯甲酸异丁酯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 21.0h， 生成 (2S,3S)-3-(N'-{(2S,3R)-2-[(S)-2-((2S,3S)-2-Benzyloxycarbonylamino-3-methyl-pentanoylamino)-4-tert-butoxycarbonyl-butyrylamino]-3-hydroxy-butyryl}-N-tert-butoxycarbonylmethyl-hydrazinocarbonyl)-oxirane-2-carboxylic acid benzyl ester
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Aza-Peptide Epoxides as Selective and Potent Inhibitors of Caspases-1, -3, -6, and -8

  摘要：

  Aza-peptide epoxides, a novel class of irreversible protease inhibitors, are specific for the clan CD cysteine proteases. Aza-peptide epoxides with an aza-Asp residue at PI are excellent irreversible inhibitors of caspases-1, -3, -6, and -8 with second-order inhibition rates up to 1910 000 M-1 s(-1). In general, the order of reactivity of aza-peptide epoxides is S'S > R,R > trans > cis. Interestingly, some of the R,R epoxides while being less potent are actually more selective than the S,S epoxides. Our aza-peptide epoxides designed For caspases are stable, potent, and specific inhibitors, as they show little to no inhibition of other proteases such as the aspartyl proteases porcine pepsin, human cathepsin D, plasmepsin 2 from P. falciparum, HIV-1 protease, and the secreted aspartic proteinase 2 (SAP-2) from Candida albicans; the serine proteases granzyme B and alpha-chymotrypsin; and the cysteine proteases cathepsin B and papain (clan CA), and legumain (clan CD).

  DOI：

  10.1021/jm0305016
• 作为产物：
  描述：

  (2S,3R)-2-[(S)-2-((2S,3S)-2-Benzyloxycarbonylamino-3-methyl-pentanoylamino)-4-tert-butoxycarbonyl-butyrylamino]-3-hydroxy-butyric acid methyl ester 在 肼 作用下， 以 甲醇 为溶剂， 反应 16.0h， 以91%的产率得到Cbz-Ile-Glu(O-t-Bu)-Thr-NHNH2
  参考文献：
  名称：

  设计，合成和评估作为caspases-2，-3，-6，-7，-8，-9和-10选择性和有效抑制剂的氮杂肽Michael受体。

  摘要：

  氮杂肽迈克尔受体是一类新颖的抑制剂，对caspases-2，-3，-6，-7，-8，-9和-10具有特异性。二阶速率常数约为10（6）M（-1）s（-1）。氮杂肽迈克尔受体抑制剂18t（Cbz-Asp-Glu-Val-AAsp-trans-CH = CH-CON（CH（2）-1-Naphth）（2）是最有效的化合物，它抑制caspase-3 ak（2）值为5620000 M（-1）s（-1）。抑制剂18t对caspase-3的选择性比caspases-2，-6高13700、190、6.4、594、37500和173倍（分别为-7，-8，-9和-10），以caspase特异性序列设计的氮杂肽Michael受体具有选择性，并且与氏族CA半胱氨酸蛋白酶（如木瓜蛋白酶，组织蛋白酶B和钙蛋白酶）没有任何交叉反应性。

  DOI：

  10.1021/jm0601405

文献信息

• Design, Synthesis, and Evaluation of Aza-Peptide Michael Acceptors as Selective and Potent Inhibitors of Caspases-2, -3, -6, -7, -8, -9, and -10
  作者：Özlem Doǧan Ekici、Zhao Zhao Li、Amy J. Campbell、Karen Ellis James、Juliana L. Asgian、Jowita Mikolajczyk、Guy S. Salvesen、Rajkumar Ganesan、Stjepan Jelakovic、Markus G. Grütter、James C. Powers

  DOI：10.1021/jm0601405

  日期：2006.9.1

  novel class of inhibitors that are potent and specific for caspases-2, -3, -6, -7, -8, -9, and -10. The second-order rate constants are in the order of 10(6) M(-1) s(-1). The aza-peptide Michael acceptor inhibitor 18t (Cbz-Asp-Glu-Val-AAsp-trans-CH=CH-CON(CH(2)-1-Naphth)(2) is the most potent compound and it inhibits caspase-3 with a k(2) value of 5620000 M(-1) s(-1). The inhibitor 18t is 13700, 190

  氮杂肽迈克尔受体是一类新颖的抑制剂，对caspases-2，-3，-6，-7，-8，-9和-10具有特异性。二阶速率常数约为10（6）M（-1）s（-1）。氮杂肽迈克尔受体抑制剂18t（Cbz-Asp-Glu-Val-AAsp-trans-CH = CH-CON（CH（2）-1-Naphth）（2）是最有效的化合物，它抑制caspase-3 ak（2）值为5620000 M（-1）s（-1）。抑制剂18t对caspase-3的选择性比caspases-2，-6高13700、190、6.4、594、37500和173倍（分别为-7，-8，-9和-10），以caspase特异性序列设计的氮杂肽Michael受体具有选择性，并且与氏族CA半胱氨酸蛋白酶（如木瓜蛋白酶，组织蛋白酶B和钙蛋白酶）没有任何交叉反应性。
• Design, Synthesis, and Evaluation of Aza-Peptide Epoxides as Selective and Potent Inhibitors of Caspases-1, -3, -6, and -8
  作者：Karen Ellis James、Juliana L. Asgian、Zhao Zhao Li、Özlem Doǧan Ekici、John R. Rubin、Jowita Mikolajczyk、Guy S. Salvesen、James C. Powers

  DOI：10.1021/jm0305016

  日期：2004.3.1

  Aza-peptide epoxides, a novel class of irreversible protease inhibitors, are specific for the clan CD cysteine proteases. Aza-peptide epoxides with an aza-Asp residue at PI are excellent irreversible inhibitors of caspases-1, -3, -6, and -8 with second-order inhibition rates up to 1910 000 M-1 s(-1). In general, the order of reactivity of aza-peptide epoxides is S'S > R,R > trans > cis. Interestingly, some of the R,R epoxides while being less potent are actually more selective than the S,S epoxides. Our aza-peptide epoxides designed For caspases are stable, potent, and specific inhibitors, as they show little to no inhibition of other proteases such as the aspartyl proteases porcine pepsin, human cathepsin D, plasmepsin 2 from P. falciparum, HIV-1 protease, and the secreted aspartic proteinase 2 (SAP-2) from Candida albicans; the serine proteases granzyme B and alpha-chymotrypsin; and the cysteine proteases cathepsin B and papain (clan CA), and legumain (clan CD).