N-(iodoacetyl)-D-alanyl-D-alanine

• 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: N-(iodoacetyl)-D-alanyl-D-alanine
• 英文别名: (2R)-2-[[(2R)-2-[(2-iodoacetyl)amino]propanoyl]amino]propanoic acid
• 化学式: C₈H₁₃IN₂O₄
• 分子量: 328.107
• InChiKey: KBRHNNVSMOSLFC-RFZPGFLSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  95.5
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (R)-2-(2-Amino-acetylamino)-3-mercapto-propionic acid 、 N-(iodoacetyl)-D-alanyl-D-alanine 在 sodium carbonate 作用下， 反应 7.0h， 以38%的产率得到2-(N-glycyl-L-cysteinyl)acetyl-D-alanyl-D-alanine
  参考文献：
  名称：

  Synthesis and Evaluation of New Substrate Analogues of Streptomyces R61 dd-Peptidase:  Dissection of a Specific Ligand

  摘要：

  Good substrates of the Streptomyces R61 DD-peptidase, such as glycyl-L-alpha-amino-epsilon-pimelyl-D-alanyl-D-alanine, 1 (Anderson, J. W.; Pratt, R. F. Biochemistry 2000,39,12200-12209), contain the glycyl-L-alpha-amino-E-pimelyl side chain. A number of thia variants of this structure have been synthesized by means of a disconnection strategy whereby the appropriate thiols were reacted with either acryloyl-D-alanyl-D-alanine or haloalkanoyl-D-alanyl-D-alanines. Kinetics studies of the hydrolysis of these compounds by the R61 DD-peptidase showed that the presence of the N-terminal glycylammonium ion and the pimelyl-alpha-carboxylate are very important for efficient catalysis. The results of deletion of the C-terminal D-alanine indicate a promising direction toward new inhibitors. Shorter (one methylene less) and longer (one methylene more) analogues of 1 are also poor substrates. Molecular modeling and dynamics studies suggest that the higher mobility of the active site residues and the modified substrates in enzyme-substrate complexes may be the dominant factor in this loss of reactivity. The general conclusion is that essentially all of the structural elements of the side chain of 1 are required to produce a good substrate. This result has important implications for the design of inhibitors of DD-peptidases.

  DOI：

  10.1021/jo048885a
• 作为产物：
  描述：

  D-丙氨酰-D-丙氨酸 、 氯化碘乙酸 在 sodium carbonate 作用下， 反应 1.5h， 以80%的产率得到N-(iodoacetyl)-D-alanyl-D-alanine
  参考文献：
  名称：

  Synthesis and Evaluation of New Substrate Analogues of Streptomyces R61 dd-Peptidase:  Dissection of a Specific Ligand

  摘要：

  Good substrates of the Streptomyces R61 DD-peptidase, such as glycyl-L-alpha-amino-epsilon-pimelyl-D-alanyl-D-alanine, 1 (Anderson, J. W.; Pratt, R. F. Biochemistry 2000,39,12200-12209), contain the glycyl-L-alpha-amino-E-pimelyl side chain. A number of thia variants of this structure have been synthesized by means of a disconnection strategy whereby the appropriate thiols were reacted with either acryloyl-D-alanyl-D-alanine or haloalkanoyl-D-alanyl-D-alanines. Kinetics studies of the hydrolysis of these compounds by the R61 DD-peptidase showed that the presence of the N-terminal glycylammonium ion and the pimelyl-alpha-carboxylate are very important for efficient catalysis. The results of deletion of the C-terminal D-alanine indicate a promising direction toward new inhibitors. Shorter (one methylene less) and longer (one methylene more) analogues of 1 are also poor substrates. Molecular modeling and dynamics studies suggest that the higher mobility of the active site residues and the modified substrates in enzyme-substrate complexes may be the dominant factor in this loss of reactivity. The general conclusion is that essentially all of the structural elements of the side chain of 1 are required to produce a good substrate. This result has important implications for the design of inhibitors of DD-peptidases.

  DOI：

  10.1021/jo048885a

文献信息

• Synthesis and Evaluation of New Substrate Analogues of <i>Streptomyces</i> R61 <scp>dd</scp>-Peptidase:  Dissection of a Specific Ligand
  作者：Rajesh Nagarajan、R. F. Pratt

  DOI：10.1021/jo048885a

  日期：2004.10.1

  Good substrates of the Streptomyces R61 DD-peptidase, such as glycyl-L-alpha-amino-epsilon-pimelyl-D-alanyl-D-alanine, 1 (Anderson, J. W.; Pratt, R. F. Biochemistry 2000,39,12200-12209), contain the glycyl-L-alpha-amino-E-pimelyl side chain. A number of thia variants of this structure have been synthesized by means of a disconnection strategy whereby the appropriate thiols were reacted with either acryloyl-D-alanyl-D-alanine or haloalkanoyl-D-alanyl-D-alanines. Kinetics studies of the hydrolysis of these compounds by the R61 DD-peptidase showed that the presence of the N-terminal glycylammonium ion and the pimelyl-alpha-carboxylate are very important for efficient catalysis. The results of deletion of the C-terminal D-alanine indicate a promising direction toward new inhibitors. Shorter (one methylene less) and longer (one methylene more) analogues of 1 are also poor substrates. Molecular modeling and dynamics studies suggest that the higher mobility of the active site residues and the modified substrates in enzyme-substrate complexes may be the dominant factor in this loss of reactivity. The general conclusion is that essentially all of the structural elements of the side chain of 1 are required to produce a good substrate. This result has important implications for the design of inhibitors of DD-peptidases.