Regioselective enzymatic acylation as a tool for producing solution-phase combinatorial libraries

被引:56
作者
Mozhaev, VV
Budde, CL
Rich, JO
Usyatinsky, AY
Michels, PC
Khmelnitsky, YL
Clark, DS
Dordick, JS
机构
[1] EnzyMed Inc, Iowa City, IA 52242 USA
[2] Univ Calif Berkeley, Dept Chem Engn, Berkeley, CA 94720 USA
[3] Univ Iowa, Dept Chem & Biochem Engn, Iowa City, IA 52242 USA
[4] Univ Iowa, Ctr Biocatalysis & Bioproc, Iowa City, IA 52242 USA
关键词
D O I
10.1016/S0040-4020(98)00129-X
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
A simple combinatorial strategy for sequential regioselective enzymatic acylation of multifunctional lead compounds has been developed and demonstrated using a polyhydroxylated flavonoid, bergenin, as a model. The approach is based on the ability of different enzymes to regioselectively acylate different sites on a lead molecule without affecting other similar functional groups. In sharp contrast to enzymatic acylation, conventional chemical acylation methods showed almost complete lack of regioselectivity. The enzymatic strategy was applied successfully to produce a solution phase combinatorial library of 167 distinct selectively acylated derivatives of bergenin on a robotic workstation in a 96-well plate format. General applicability of the automated combinatorial biocatalysis strategy is discussed. (C) 1998 Published by Elsevier Science Ltd. All rights reserved.
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页码:3971 / 3982
页数:12
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