Expanded structural and stereospecificity in peptide synthesis with chemically modified mutants of subtilisin

被引:17
作者
Khumtaveeporn, K [1 ]
DeSantis, G [1 ]
Jones, JB [1 ]
机构
[1] Univ Toronto, Dept Chem, Toronto, ON M5S 3H6, Canada
关键词
D O I
10.1016/S0957-4166(99)00255-4
中图分类号
O61 [无机化学];
学科分类号
070301 ; 081704 ;
摘要
Employing the strategy of combined site directed mutagenesis and chemical modification, we previously generated chemically modified mutant enzymes (CMMs) of subtilisin Bacillus lentus (SBL). We now report the use of these SBL-CMMs for peptide coupling reactions. The SBL-CMMs exhibit dramatically altered substrate specificity, including the acceptance of D-amino acid acyl donors, generating dipeptides containing D-Phe, D-Ala and D-Glu in up to 66% yield, which was not possible using wild-type SBL (WT-SBL). In addition, SBL-CMMs accommodate alpha-branched amino acids such as L-Ala-NH2 as acyl accepters in their S-1' pockets, which WT-SBL will not. (C) 1999 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:2563 / 2572
页数:10
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