In recent years, stereochemistry has become an integral part of drug discovery and design resulting in an ever-increasing preference for single-enantiomer drugs. Therefore, it is important to study stereoselective events between chiral drugs and structural and functional proteins of the human body. This study is designed to identify the UDP-glucuronosyltransferases (UGTs) responsible for the stereoselective transformation of chiral substrates. The application of drug-like enantiopure molecular probes will identify the UGTs displaying stereoselective glucuronidation. The binding and glucuronic acid-transfer reaction of chiral model substrates and drugs will be studied to achieve better understanding of stereoselective events during catalytic glucuronidation on the molecular level. This study is assumed to provide sufficient data for the establishment of computational models capable of predicting the UGT-catalyzed glucuronidation of chiral drugs and drug candidates. The design of chiral UGT isoform-specific reversible and irreversible inhibitors will be studied, enabling the identification of the catalytic site of UGTs. Finally, this approach will be extended to other transfer enzymes of the human metabolic machinery, such as sulfotransferases and acyltransferases, to study the fundamental stereochemistry of the respective conjugation reactions.
Vastaava tutkija
Yli-Kauhaluoma Jari, Helsingin yliopisto, Farmasian tiedekunta, Farmaseuttisen kemian osasto Hankkeen kesto 2006 - 2007
Asiasanat
UGT, UDP-glucuronosyltransferase, stereochemistry, chirality, stereoselectivity, inhibitor, substrate, medicinal chemistry, metabolism
Hankkeen vaihe: päättynyt
HUOM! Tämä tutkimushankekuvaus on tuotettu Hankehaaviin Helsingin yliopiston TUHTI-tutkimustietojärjestelmästä, jota ei enää ylläpidetä. Tarkista ajantaiset tutkimushanketiedot Helsingin yliopiston TUHAT-järjestelmästä.
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