| 1608081-22-6

• 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
• CAS: 1608081-22-6
• 化学式: C₂₄H₂₉N₃O₆
• 分子量: 456.5
• InChiKey: WVNDGORMRPEOSW-RIQWGZLTSA-N

反应信息

• 作为反应物：
  描述：

  在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 1.5h， 以54%的产率得到
  参考文献：
  名称：

  Hemiacetal stabilization in a chymotrypsin inhibitor complex and the reactivity of the hydroxyl group of the catalytic serine residue of chymotrypsin

  摘要：

  The aldehyde inhibitor Z-Ala-Ala-Phe-CHO has been synthesized and shown by C-13-NMR to react with the active site serine hydroxyl group of alpha-chymotrypsin to form two diastereomeric hemiacetals. For both hemiacetals oxyanion formation occurs with a pK(a) value of similar to 7 showing that chymotrypsin reduces the oxyanion pKa values by similar to 5.6 pk(a) units and stabilizes the oxyanions of both diastereoisomers by similar to 32 kJ mol(-1). As pH has only a small effect on binding we conclude that oxyanion formation does not have a significant effect on binding the aldehyde inhibitor. By comparing the binding of Z-Ala-Ala-Phe-CHO with that of Z-Ala-Ala-Phe-H we estimate that the aldehyde group increases binding similar to 100 fold. At pH 7.2 the effective molarity of the active site serine hydroxy group is -6000 which is similar to 7 x less effective than with the corresponding glyoxal inhibitor. Using H-1-NMR we have shown that at both 4 and 25 degrees C the histidine pK(a) is similar to 7.3 in free chymotrypsin and it is raised to similar to 8 when Z-Ala-Ala-Phe-CHO is bound. We conclude that oxyanion formation only has a minor role in raising the histidine pKa and that the aldehyde hydrogen must be replaced by a larger group to raise the histidine PKa> 10 and give stereospecific formation of tetrahedral intermediates. The results show that a large increase in the pKa of the active site histidine is not needed for the active site serine hydroxyl group to have an effective molarity of 6000. (C) 2014 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.bbapap.2014.03.008