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

✍ Scribed by Vadim V. Mozhaev; Cheryl L. Budde; Joseph O. Rich; Alexander Ya. Usyatinsky; Peter C. Michels; Yuri L. Khmelnitsky; Douglas S. Clark; Jonathan S. Dordick

• Book ID: 104208490
• Publisher: Elsevier Science
• Year: 1998
• Tongue: French
• Weight: 659 KB
• Volume: 54
• Category: Article
• ISSN: 0040-4020
• DOI: 10.1016/s0040-4020(98)00129-x

✦ Synopsis

A simple combinatorial strategy for sequential regioselective enzymatic acylation of multifunctional lead compounds has been developed and demonstrated using a polyhydrexylated 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 acylatinn 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.