N-tert-butyloxycarbonyl-L-valyl-L-lysyl-L-leucine methylester | 150650-94-5

• 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-tert-butyloxycarbonyl-L-valyl-L-lysyl-L-leucine methylester
• 英文别名: Boc-Val-Lys-Leu-OMe；methyl (2S)-2-[[(2S)-6-amino-2-[[(2S)-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoyl]amino]hexanoyl]amino]-4-methylpentanoate
• CAS: 150650-94-5
• 化学式: C₂₃H₄₄N₄O₆
• 分子量: 472.626
• InChiKey: BVOQXFABVAGMQR-BZSNNMDCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  33
• 可旋转键数：
  16
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  149
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-tert-butyloxycarbonyl-L-valyl-L-lysyl-L-leucine methylester 在 sodium cyanoborohydride 、 碳酸氢钠 、 一水合肼 、 溶剂黄146 作用下， 以 乙醇 、 氯仿 、 溶剂黄146 、 乙酸乙酯 为溶剂， 反应 77.0h， 生成 1-(N-tert-butyloxycarbonyl-L-valyl-N_ε-methyloxycarbonyl-L-lysyl-L-leucyl)-2-(4-hydroxybenzyl)-2-bromoacetyl hydrazine
  参考文献：
  名称：

  Synthesis and inhibiting activities of 1-peptidyl-2-haloacetyl hydrazines toward cathepsin B and calpains

  摘要：

  Twenty-four 1-peptidyl-2-haloacetyl hydrazines which can be considered azapeptide halomethanes were synthesized and tested as models of cathepsin B, calpain I and calpain II inhibitors. Reagents designed for cathepsin B inactivation include Z-Tyr, Z-Tyr(I) and Z-Leu-Leu attached to an alpha-azaglycine or alpha-azaalanine unit in P1. By use of kinetic analysis, they proved to irreversibly inactivate cathepsin B via a reversible enzyme-inhibitor intermediate. Second-order rate constants in the range 725-306 000 M-1s-1 were found for cathepsin B inactivation, with no more than 7 500 M-1s-1 for calpain II. K(I) for the reversible EI adducts ranged from 11 to 0.06 muM for cathepsin B. Structure of the possible reversible EI complex is proposed and used to discuss the effects of structural variation of the inhibitors on the kinetic parameters of inactivation. I-Peptidyl-2-haloacetyl hydrazines designed for calpain inactivation include Boc-Val-(N(epsilon)-carbomethoxy)Lys-Leu, Boc-Val-Lys(N(epsilon)-Z)-Leu, Boc-Val-Lys(N(epsilon)-Tos)-Leu and Z-Leu-Leu attached to an alpha-azatyrosine unit in P1. They gave poor results. Title compounds proved to be selective for cysteine proteases, since no inhibiting activity could be detected toward trypsin, chymotrypsin and porcine pancreatic elastase at 0.1 mM concentration. Relatively low aspecific alkylating properties were also demonstrated in tests using glutathione as the nucleophile.

  DOI：

  10.1016/0223-5234(93)90147-7
• 作为产物：
  描述：

  N-tert-butyloxycarbonyl-L-valyl-N_ε-benzyloxycarbonyl-L-lysyl-L-leucine methylester 在 palladium on activated charcoal 氢气 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以100%的产率得到N-tert-butyloxycarbonyl-L-valyl-L-lysyl-L-leucine methylester
  参考文献：
  名称：

  Synthesis and inhibiting activities of 1-peptidyl-2-haloacetyl hydrazines toward cathepsin B and calpains

  摘要：

  Twenty-four 1-peptidyl-2-haloacetyl hydrazines which can be considered azapeptide halomethanes were synthesized and tested as models of cathepsin B, calpain I and calpain II inhibitors. Reagents designed for cathepsin B inactivation include Z-Tyr, Z-Tyr(I) and Z-Leu-Leu attached to an alpha-azaglycine or alpha-azaalanine unit in P1. By use of kinetic analysis, they proved to irreversibly inactivate cathepsin B via a reversible enzyme-inhibitor intermediate. Second-order rate constants in the range 725-306 000 M-1s-1 were found for cathepsin B inactivation, with no more than 7 500 M-1s-1 for calpain II. K(I) for the reversible EI adducts ranged from 11 to 0.06 muM for cathepsin B. Structure of the possible reversible EI complex is proposed and used to discuss the effects of structural variation of the inhibitors on the kinetic parameters of inactivation. I-Peptidyl-2-haloacetyl hydrazines designed for calpain inactivation include Boc-Val-(N(epsilon)-carbomethoxy)Lys-Leu, Boc-Val-Lys(N(epsilon)-Z)-Leu, Boc-Val-Lys(N(epsilon)-Tos)-Leu and Z-Leu-Leu attached to an alpha-azatyrosine unit in P1. They gave poor results. Title compounds proved to be selective for cysteine proteases, since no inhibiting activity could be detected toward trypsin, chymotrypsin and porcine pancreatic elastase at 0.1 mM concentration. Relatively low aspecific alkylating properties were also demonstrated in tests using glutathione as the nucleophile.

  DOI：

  10.1016/0223-5234(93)90147-7