PROTEASE-CATALYZED PEPTIDE-SYNTHESIS - BASIC PRINCIPLES, NEW SYNTHESIS STRATEGIES AND MEDIUM ENGINEERING

被引:38
作者
JAKUBKE, HD
机构
[1] Leipzig University, Faculty of Biosciences, Pharmacology and Psychology, Department of Biochemistry, Leipzig, D-04103
关键词
ENZYMATIC PEPTIDE SYNTHESIS; PROTEASES; ACYL-TRANSFER; MODIFIED ENZYMES;
D O I
10.1002/jccs.199400049
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The application of enzymes to perform selective transformations is the central aim of industrial biocatalysis. Since a simple handled C-N ligase is not available, the only alternative of general practical interest for enzymatic peptide bond formation are proteases due to the principle of microscopic reversibility. The stereo- and regiospecificity of proteases, which guarantee racemization-free segment condensation and require only minimal side-chain protection, are significant for preparative purposes. Unfortunately, proteases are not perfect acyltransferases. Both unwanted proteolytic side reactions and the hydrolysis of the acyl-enzyme in the kinetic approach are the major problems in enzymatic peptide synthesis. The object of this paper was to demonstrate several new synthesis strategies including medium engineering that enables one to bypass unfavorable reaction routes. Planning and optimization of enzymatic peptide synthesis require the S' subsite mapping of proteases and the knowledge of additional basic parameters that determine the reaction course.
引用
收藏
页码:355 / 370
页数:16
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