Solid-phase peptide synthesis by ion-paired α-chymotrypsin in nonaqueous media
Solid-phase peptide synthesis by ion-paired α-chymotrypsin in nonaqueous media
复制标题
DOI：
10.1002/bit.10536
复制
发表时间：
2003-03-30
影响因子：
3.8
通讯作者：
Clark, DS
中科院分区：
文献类型：
--
作者：
Altreuter, DH;Dordick, JS;Clark, DS
使用溶解在有机溶剂中的 AOT 离子对 α-胰凝乳蛋白酶在低水介质中固相合成二肽。使用多种溶剂和水活度的系统变化a(w)来检查N-α-苄氧基羰基-L-苯丙氨酸甲酯(Z-Phe-OMe)和亮氨酸之间的偶联速率作为固相和溶液反应的反应介质的函数。在溶液中，在给定溶剂中观察到的最大反应速率通常与疏水性测量相关，例如 1-辛醇/水分配系数 (log P) 的对数和希尔德布兰德溶解度参数。溶液相合成的最大速率（13 mmol/h g-酶）是在 a(w) 为 0.30 的 90/10 (v/v) 异辛烷/四氢呋喃溶剂混合物中获得的。对于从固相亮氨酸残基合成二肽而言，最高合成速率（0.14-1.3 mmol/h g-酶）仅限于溶剂环境，这些环境落在溶剂参数空间的突然定义区域内（例如，log P > 2.3 和归一化电子接受指数）
Solid-phase synthesis of dipeptides in low-water media was achieved using AOT ion-paired alpha-chymotrypsin solubilized in organic solvents. Multiple solvents and systematic variation of water activity, a(w) were used to examine the rate of coupling between N-alpha-benzyloxycarbonyl-L-phenylalanine methyl ester (Z-Phe-OMe) and leucine as a function of the reaction medium for both solid-phase and solution-phase reactions. In solution, the observed maximum reaction rate in a given solvent generally correlated with measures of hydrophobicity such as the log of the 1-octanol/water partitioning coefficient (log P) and the Hildebrand solubility parameter. The maximum rate for solution-phase synthesis (13 mmol/h g-enzyme) was obtained in a 90/10 (v/v) isooctane/tetrahydrofuran solvent mixture at an a(w) of 0.30. For the synthesis of dipeptides from solid-phase leucine residues, the highest synthetic rates (0.14-1.3 mmol/h g-enzyme) were confined to solvent environments that fell inside abruptly defined regions of solvent parameter space (e.g., log P > 2.3 and normalized electron acceptance index