Synthesis and evaluation of a model for the so-called "charge-relay" system of the serine esterases.
Synthesis and evaluation of a model for the so-called "charge-relay" system of the serine esterases.
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DOI：
10.1021/ja00815a028
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发表时间：
1974-04
影响因子：
15
通讯作者：
G. Rogers;T. C. Bruice
中科院分区：
文献类型：
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作者：
G. Rogers;T. C. Bruice
本文介绍了丝氨酸酯酶Asp-His-Ser三联体模型化合物的合成、酸碱性质和水解反应。发现乙酸苯酯VII、VIII和IX [未取代和取代的2-（2 ′-羟基苯基）咪唑的O-乙酰基酯的4（5）-甲基-5（4）-二甲基乙酸衍生物]通过先前对不含羧基官能团的酯确定的相同机理途径水解。也就是说，虽然在酯键处观察到咪唑基一般和一般碱辅助的H2O攻击，但没有检测到0-> N乙酰基转移到咪唑阴离子。所提供的证据显示三倍的速率增强，归因于羧基，并且与咪唑基通用碱辅助H2O攻击酯VII和IX有关。当IX转移到含有但6%H2O的非质子溶剂（CH 3CN）中时，没有观察到咪唑基或羧基的催化作用的增强。酚类IV、V和VI（VII、VIII和IX的酚类水解产物）在HjO和较低介电常数的水-有机混合溶剂中的酸碱性质表明，羧基和咪唑基碱强度没有逆转。即使在96%的二氧六环中，pXimn+» pXcooh-这些发现根据已经提出的pX进行了讨论。丝氨酸酯酶活性位点的氨基和残基的催化三联体的值。
The synthesis, arid-base properties, and hydrolytic reactions of model compounds for the Asp-His-Ser triad of the serine esterases are presented. The phenyl acetates Vil, VIII, and IX [4 (5)-methyl-5 (4)-dimethylacetic acid derivatives of O-acetyl esters of unsubstituted and substituted 2-(2'-hydroxyphenyl) imidazoles] were found to hydrolyze via the same mechanistic pathways previously determined for the esters without the carboxyl function. That is, while both imidazolyl general arid and general base assisted H2O attack at the ester bond are observed, no 0-> N acetyl transfer to the imidazole anion was detected. Evidence presented shows a threefold rate enhance-ment, attributable to the carboxyl group, andassociated with the imidazolyl general base assisted H20 attack upon esters VII and IX. When IX is transferred to an aprotic solvent (CH3CN) containing but 6% H20, no enhancement of the catalytic role of either the imidazolyl or the carboxyl group is observed. The acid-base properties of the phenols IV, V, and VI (phenolic hydrolysis products of VII, VIII, and IX) in both HjO and aqueous-organic mixed solvents of lower dielectric show that there is no inversion of the carboxyl and imidazolyl base strengths. Even in 96% dioxane, pXimn+» pXcooh-These findings are discussed in light of what has been proposed for the pX. values of the catalytic triad of amino arid residues at the active site of the serine esterases.