Dynamic catalytic screening of hydrolase substrates from adaptive combinatorial thiolester libraries

ORGN 231

Rikard Larsson, rlarsson@kth.se, Marcus Angelin, angelin@kth.se, Pornrapee Vongvilai, pornrapee@kth.se, and Olof Ramstrom, ramstrom@kth.se. Department of Chemistry, Royal Institute of Technology, Teknikringen 30, S-100 44 Stockholm, Sweden
Adaptive combinatorial thiolester libraries were efficiently generated from pools of thiols and thiolesters having different acyl functionalities, through reversible transthiolesterification in aqueous media at neutral pH. The dynamic features of the library generation were investigated, and the libraries were screened against different hydrolases, demonstrating the dynamic catalytic screening of their substrates from the constituents. The best substrates for the enzymes were easily identified, whereas other constituents showed lower efficiency or were inactive. The results show that transthiolesterification is a useful method to generate dynamic libraries, and that the dynamic catalytic screening concept is highly valuable for substrate identification.
 

Asymmetric Reactions and Syntheses, Metal-Mediated Reactions, Combinatorial, Parallel, and Solid-Phase Chemistry
8:00 PM-10:00 PM, Sunday, 10 September 2006 Moscone Center -- Hall D, Poster

Sci-Mix
8:00 PM-10:00 PM, Monday, 11 September 2006 Moscone Center -- Hall D, Sci-Mix

Division of Organic Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006