Application of various inverse substrates to thrombin-catalyzed peptide synthesis
Application of various inverse substrates to thrombin-catalyzed peptide synthesis
复制标题
各种反向底物在凝血酶催化肽合成中的应用
DOI：
10.1248/cpb.47.444
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发表时间：
1999
影响因子：
1.7
通讯作者：
K. Tanizawa
中科院分区：
文献类型：
--
作者：
H. Sekizaki;K. Itoh;E. Toyota;K. Tanizawa
凝血酶催化的肽合成已经使用九个系列的反向底物进行了研究，即，对脒基苯基、对胍基苯基和间胍基苯基、对胍基甲基苯基和间胍基甲基苯基以及衍生自N α -（叔丁氧基羰基）氨基酸的胍基萘酯的四位异构体作为酰基供体组分。这些底物根据其对凝血酶的反应分为两类。一组包括对脒基和对胍基苯基酯，其经历较少的对映选择性偶联反应。被分类为另一组的底物是间胍基苯基、对-和间-（胍基甲基）苯基以及涉及对映选择性偶联反应的胍基萘酯的四位异构体。因此，L-系列的氨基酸残基（在本例中为N α -Boc-L-Ala）很容易偶联，通过将它们分配给任何一种反向底物而得到肽。通过改变有机溶剂、pH值和酰基受体浓度，研究了偶联反应的最佳条件。发现所得产物的酶促水解可忽略不计。
Thrombin-catalyzed peptide synthesis has been studied using nine series of inverse substrates, i.e., p-amidinophenyl, p- and m-guanidinophenyl, p- and m-(guanidinomethyl)phenyl, and four position isomers of guanidinonaphthyl esters derived from N α -(tert-butyloxycarbonyl)amino acid as acyl donor components. These substrates were classified into two types with respect to their response to thrombin. One group includes p-amidino- and p-guanidinophenyl esters, which undergo less enantioselective coupling reaction. Substrates classified into the other group are m-guanidinophenyl, p- and m-(guanidinomethyl)phenyl, and four position isomers of guanidinonaphthyl esters which are involved in the enantioselective coupling reaction. Thus amino acid residues of L-series (in the present case; N α -Boc-L-Ala) are readily coupled to afford peptides by assigning them to either of the inverse substrates. The optimum condition for the coupling reaction was studied by changing organic solvent, pH, and acyl acceptor concentration. It was found that the enzymatic hydrolysis of the resulting product was negligible.