Dynamic Combinatorial Thiolester Libraries for Efficient Catalytic Self-Screening of Hydrolase Substrates
2006 (English)In: European Journal of Organic Chemistry, ISSN 1434-193X, E-ISSN 1099-0690, no 1, 285-291 p.Article in journal (Refereed) Published
Dynamic combinatorial thiolester libraries were efficiently generated from pools of thiols and 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 acetylcholinesterase, clearly demonstrating the catalytic self-screening of its substrates from the constituents. Acetyl- and propionylthiocholine were easily identified as the best substrates for the enzyme, whereas other constituents showed lower efficiency or were inactive. A range of hydrolases was furthermore screened for rapid substrate identification, clearly demonstrating the differences in selectivity. The results show that transthiolesterification is a useful method to generate dynamic libraries, and that the catalytic self -screening concept is highly valuable for substrate identification.
Place, publisher, year, edition, pages
2006. no 1, 285-291 p.
combinatorial chemistry; enzyrne catalysis; hydrolysis; transesterification
IdentifiersURN: urn:nbn:se:kth:diva-8266DOI: 10.1002/ejoc.200500699ISI: 000234237500028ScopusID: 2-s2.0-33745819380OAI: oai:DiVA.org:kth-8266DiVA: diva2:13543
QC 201008182008-04-252008-04-252010-08-18Bibliographically approved