Z-L-Ala-L-prolinal | 91650-02-1

• 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: Z-L-Ala-L-prolinal
• 英文别名: benzyl N-[(2S)-1-[(2S)-2-formylpyrrolidin-1-yl]-1-oxopropan-2-yl]carbamate
• CAS: 91650-02-1
• 化学式: C₁₆H₂₀N₂O₄
• 分子量: 304.346
• InChiKey: SQXBJJUQJZTQQJ-JSGCOSHPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  75.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (2S)-N-苄氧羰基-2-吡咯烷甲醛 在 palladium on activated charcoal 盐酸 、 聚合甲醛 、 氢气 、 sodium acetate 、 三乙胺 作用下， 以 甲醇 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 30.12h， 生成 Z-L-Ala-L-prolinal
  参考文献：
  名称：

  Synthesis and structure of prolinal-containing peptides, and their use as specific inhibitors of prolyl endopeptidases.

  摘要：

  肽醛是丝氨酸和半胱氨酸蛋白酶的强效抑制剂。在本研究工作中，合成了含羧基末端脯氨醛的N-苄氧羰基（Z）二肽，作为脯氨酰内肽酶的抑制剂。由于通过质子核磁共振（1H-NMR）光谱法未检测到醛质子，因此为这些肽提出了一个环状结构。具有Z-L-X-L-脯氨醛结构的化合物是海鞘Halocynthia roretzi和黄杆菌Flavobacterium meningosepticum的脯氨酰内肽酶的强效抑制剂。其效力顺序为Z-L-Val-L-脯氨醛≈Z-L-Ile-L-脯氨醛>Z-L-Phe-L-脯氨醛>Z-L-Ala-L-脯氨醛，IC50值为10-8-10-6 M，对两种酶均有效。将醛转化为醇或酸部分会导致抑制活性显著降低。Z-L-Phe-L-脯氨醛的差向异构体抑制作用较弱。这一结果与黄杆菌酶对其底物的报道立体特异性不一致。这表明开放型物种优先结合到酶活性位点。

  DOI：

  10.1248/cpb.34.2931

文献信息

• Anti-amnestic agent
  申请人：Kabushiki Kaisha Yakult Honsha

  公开号：US04687778A1

  公开（公告）日：1987-08-18

  An anti-amnestic agent which comprises as an active ingredient thereof at least one prolinal derivative of the general formula: ##STR1## wherein A is a protective groups for amino group in the field of amino acid chemistry and X is a residue of an amino acid, in a pharmacologically active amount together with an exipient. This agent is less toxic and can be safely administered to patients orally or intravenously for the remedy of memory disorder.

  一种抗遗忘剂，其活性成分至少包括一种普罗林酰衍生物，其通式如下：##STR1## 其中A是氨基酸化学领域中氨基保护基，X是氨基酸残基，与赋形剂一起以药理学有效量形式使用。该剂量毒性较小，可安全地口服或静脉注射给患者治疗记忆障碍。
• An anti-amnestic agent
  申请人：KABUSHIKI KAISHA YAKULT HONSHA

  公开号：EP0154353A2

  公开（公告）日：1985-09-11

  An anti-amnestic agent which comprises as an active ingredient thereof at least one prolinal derivative of the general formula I wherein A is a protective group for amino group in the field of amino acid chemistry and X is a residue of an amino acid, in a pharmacologically active amount together with an excipient. This agent is less toxic and can safely be administered to patients orally or intravenously for the remedy of memory disorder.

  一种抗失忆药剂，其有效成分包括至少一种通式 I 的脯氨酸衍生物，其中 A 是氨基酸化学领域中对氨基的保护基团，X 是氨基酸的残基，药效量与赋形剂一起使用。 这种药剂毒性较低，可安全地口服或静脉注射给患者，用于治疗记忆障碍。
• US4687778A
  申请人：——

  公开号：US4687778A

  公开（公告）日：1987-08-18
• Synthesis and structure of prolinal-containing peptides, and their use as specific inhibitors of prolyl endopeptidases.
  作者：MAKOTO NISHIKATA、HIDEYOSHI YOKOSAWA、SHIN-ICHI ISHII

  DOI：10.1248/cpb.34.2931

  日期：——

  Peptide aldehydes are potent inhibitors of serine and cysteine proteases. In the present work, N-benzyloxycarbonyl (Z) dipeptides containing prolinal at the carboxyl terminus were syntheized as inhibitors of prolyl endopeptidases. Since no aldehyde proton was detected by proton nuclear magnetic resonance (1H-NMR) spectrometry, a cyclic structure was proposed for these peptides. Compounds with a Z-L-X-L-prolinal structure were strong inhibitors of prolyl endopeptidases from the ascidian, Halocynthia roretzi, and Flavobacterium meningosepticum. The potency was in the order of Z-L-Val-L-prolinal≃Z-L-Ile-L-prolinal>Z-L-Phe-L-prolinal>Z-L-Ala-L-prolinal with IC50 values of 10-8-10-6 M order for both enzymes. Conversion of the aldehyde into an alcohol or an acid moiety resulted in a considerable decrease in the inhibitory activity. The diastereomers of Z-L-Phe-L-prolinal were much less inhibitory. This result is not compatible with the reported stereospecifity of the Flavobacterium enzyme for its substrated [T. Yoshimoto, R. Walter and D. Tsuru, J. Biol. Chem., 255, 4786 (1980)]. This implies that the open species binds preferentially to the enzyme active site.

  肽醛是丝氨酸和半胱氨酸蛋白酶的强效抑制剂。在本研究工作中，合成了含羧基末端脯氨醛的N-苄氧羰基（Z）二肽，作为脯氨酰内肽酶的抑制剂。由于通过质子核磁共振（1H-NMR）光谱法未检测到醛质子，因此为这些肽提出了一个环状结构。具有Z-L-X-L-脯氨醛结构的化合物是海鞘Halocynthia roretzi和黄杆菌Flavobacterium meningosepticum的脯氨酰内肽酶的强效抑制剂。其效力顺序为Z-L-Val-L-脯氨醛≈Z-L-Ile-L-脯氨醛>Z-L-Phe-L-脯氨醛>Z-L-Ala-L-脯氨醛，IC50值为10-8-10-6 M，对两种酶均有效。将醛转化为醇或酸部分会导致抑制活性显著降低。Z-L-Phe-L-脯氨醛的差向异构体抑制作用较弱。这一结果与黄杆菌酶对其底物的报道立体特异性不一致。这表明开放型物种优先结合到酶活性位点。