Nα-benzoyl-L-citrulline | 10334-68-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: Nα-benzoyl-L-citrulline
• 英文别名: Bz-citrulline；N-Benzoyl-L-citrullin；Benzoylcitrullin；Benzoyl-citrulline；(2S)-2-benzamido-5-(carbamoylamino)pentanoic acid
• CAS: 10334-68-6
• 化学式: C₁₃H₁₇N₃O₄
• 分子量: 279.296
• InChiKey: AQVYVXPQZVSAKM-JTQLQIEISA-N

物化性质

• 沸点：
  597.8±50.0 °C(Predicted)
• 密度：
  1.287±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  20
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  122
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  N-ALPHA-苄酰-L-精氨酸 在 alpha-酮戊二酸 、 bovine liver glutamate dehydrogenase type II 、 recombinant Giardia lamblia arginine deiminase 、 水 作用下， 生成 Nα-benzoyl-L-citrulline
  参考文献：
  名称：

  Mechanisms of catalysis and inhibition operative in the arginine deiminase from the human pathogen Giardia lamblia

  摘要：

  Giardia lamblia arginine deiminase (GlAD), the topic of this paper, belongs to the hydrolase branch of the guanidine-modifying enzyme superfamily, whose members employ Cys-mediated nucleophilic catalysis to promote deimination of L-arginine and its naturally occurring derivatives. G. lamblia is the causative agent in the human disease giardiasis. The results of RNAi/antisense RNA gene-silencing studies reported herein indicate that GlAD is essential for G. lamblia trophozoite survival and thus, a potential target for the development of therapeutic agents for the treatment of giardiasis. The homodimeric recombinant protein was prepared in Escherichia coli for in-depth biochemical characterization. The 2-domain GlAD monomer consists of a N-terminal domain that shares an active site structure (depicted by an in silico model) and kinetic properties (determined by steady-state and transient state kinetic analysis) with its bacterial AD counterparts, and a C-terminal domain of unknown fold and function. GlAD was found to be active over a wide pH range and to accept L-arginine, L-arginine ethyl ester, N-alpha-benzoyl-L-arginine, and N-omega-amino-L-arginine as substrates but not agmatine, L-homoarginine, N-alpha-benzoyl- L-arginine ethyl ester or a variety of arginine-containing peptides. The intermediacy of a Cys424-alkylthiouronium ion covalent enzyme adduct was demonstrated and the rate constants for formation (k(1) = 80 s(-1)) and hydrolysis (k(2) = 35 s(-1)) of the intermediate were determined. The comparatively lower value of the steady-state rate constant (k(cat) = 2.6 s(-1)), suggests that a step following citrulline formation is rate-limiting. Inhibition of GlAD using Cys directed agents was briefly explored. S-Nitroso-L-homocysteine was shown to be an active site directed, irreversible inhibitor whereas N omega-cyano-L-arginine did not inhibit GlAD but instead proved to be an active site directed, irreversible inhibitor of the Bacillus cereus AD. (C) 2009 Published by Elsevier Inc.

  DOI：

  10.1016/j.bioorg.2009.06.001

文献信息

• PRODUIT DE COMBINAISON POUR LE TRAITEMENT DU SURPOIDS ET/OU L'AMÉLIORATION DE LA SILHOUETTE
  申请人：Institut National de la Recherche Agronomique (INRA)

  公开号：EP2819635A1

  公开（公告）日：2015-01-07
• [EN] COMBINATION PRODUCT FOR TREATING EXCESS WEIGHT AND/OR FOR IMPROVING THE FIGURE<br/>[FR] PRODUIT DE COMBINAISON POUR LE TRAITEMENT DU SURPOIDS ET/OU L'AMÉLIORATION DE LA SILHOUETTE
  申请人：AGRONOMIQUE INST NAT RECH

  公开号：WO2013128137A1

  公开（公告）日：2013-09-06

  L'invention concerne un produit de combinaison comprenant à titre de substances actives, au moins un inhibiteur de l'enzyme HMG-CoA-réductase et la citrulline ou un composé bioéquivalent de celle-ci pour le traitement du surpoids ou de l'obésité et/ou de l'accumulation de masse grasse. L'invention concerne également un procédé de traitement cosmétique pour améliorer ou affiner la silhouette et/ou stimuler la perte de poids superflu et/ou de cellulite et/ou limiter son accumulation, comprenant l'administration d'un produit de combinaison comprenant à titre de substances actives, au moins un inhibiteur de l'enzyme HMG-CoA-réductase ou un sel physiologiquement acceptable de celle-ci, et la citrulline ou un composé bioéquivalent de celle- ci, ou l'un de leurs analogues et le renouvellement de ladite administration jusqu'à obtention de l'effet cosmétique désiré. L'invention concerne enfin l'utilisation d'un produit de combinaison tel que précédemment défini pour améliorer ou affiner la silhouette et/ou stimuler la perte de poids superflu et/ou de cellulite et/ou limiter son accumulation.
• Mechanisms of catalysis and inhibition operative in the arginine deiminase from the human pathogen Giardia lamblia
  作者：Zhimin Li、Liudmila Kulakova、Ling Li、Andrey Galkin、Zhiming Zhao、Theodore E. Nash、Patrick S. Mariano、Osnat Herzberg、Debra Dunaway-Mariano

  DOI：10.1016/j.bioorg.2009.06.001

  日期：2009.10

  Giardia lamblia arginine deiminase (GlAD), the topic of this paper, belongs to the hydrolase branch of the guanidine-modifying enzyme superfamily, whose members employ Cys-mediated nucleophilic catalysis to promote deimination of L-arginine and its naturally occurring derivatives. G. lamblia is the causative agent in the human disease giardiasis. The results of RNAi/antisense RNA gene-silencing studies reported herein indicate that GlAD is essential for G. lamblia trophozoite survival and thus, a potential target for the development of therapeutic agents for the treatment of giardiasis. The homodimeric recombinant protein was prepared in Escherichia coli for in-depth biochemical characterization. The 2-domain GlAD monomer consists of a N-terminal domain that shares an active site structure (depicted by an in silico model) and kinetic properties (determined by steady-state and transient state kinetic analysis) with its bacterial AD counterparts, and a C-terminal domain of unknown fold and function. GlAD was found to be active over a wide pH range and to accept L-arginine, L-arginine ethyl ester, N-alpha-benzoyl-L-arginine, and N-omega-amino-L-arginine as substrates but not agmatine, L-homoarginine, N-alpha-benzoyl- L-arginine ethyl ester or a variety of arginine-containing peptides. The intermediacy of a Cys424-alkylthiouronium ion covalent enzyme adduct was demonstrated and the rate constants for formation (k(1) = 80 s(-1)) and hydrolysis (k(2) = 35 s(-1)) of the intermediate were determined. The comparatively lower value of the steady-state rate constant (k(cat) = 2.6 s(-1)), suggests that a step following citrulline formation is rate-limiting. Inhibition of GlAD using Cys directed agents was briefly explored. S-Nitroso-L-homocysteine was shown to be an active site directed, irreversible inhibitor whereas N omega-cyano-L-arginine did not inhibit GlAD but instead proved to be an active site directed, irreversible inhibitor of the Bacillus cereus AD. (C) 2009 Published by Elsevier Inc.