Naslov
Evaluation of butyrylcholinesterase stereoselectivity in interaction with enantiomers of ethopropazine

Autori
Šinko, Goran ; Maraković, Nikola ; Stojan, Jure

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Book of Abstracts of the Congress of the Croatian Society of Biochemistry and Molecular Biology "The Interplay of Biomolecules", HDBMB 2014 / Katalinić, M. ; Kovarik, Z. - Zagreb : The Croatian Society of Biochemistry and Molecular Biology, 2014, 129-129

ISBN
978-953-95551-5-1

Skup
The Congress of the Croatian Society of Biochemistry and Molecular Biology "The Interplay of Biomolecules", HDBMB 2014

Mjesto i datum
Zadar, Hrvatska, 24.09.2014. - 27.09.2014

Vrsta sudjelovanja
Poster

Vrsta recenzije
Domaća recenzija

Ključne riječi
temperature effect on enzyme structure dynamics

Sažetak
Stereoselectivity of biological macromolecules originates from chiral amino acids which are building blocks for enzymes and other proteins. It is usual for enzyme to show stereoselectivity in interaction with chiral substrate or inhibitor. We studied butyrylcholinesterase (BChE, EC 3.1.1.8) stereoselectivity in interaction with enantiomers of ethopropazine. BChE is related to acetylcholinesterase (AChE, EC 3.1.1.7) which is involved in neurotransmission and they share 54% of sequence homology. BChE is involved in hydrolysis of various esters and xenobiotics which makes it useful in prodrug conversion, i.e. bambuterol used in the treatment of asthma. Ethopropazine is a chiral drug used in treatment of Parkinson’s disease in form of a racemate, an equimolar mixture of individual enantiomers. We performed a series of BChE activity measurements in which we used low, mid and high substrate concentrations (100 µM, 1 mM and 100 mM) and performed BChE inhibition with addition of racemic and enantiomeric pure ethopropazine into the reaction mixture to evaluate BChE stereoselectivity. We evaluated stereoselectivity of a free enzyme and different enzyme-substrate complexes by using various substrate concentrations. Different BChE-substrate complexes occur at high substrate concentration well above KM value for acetylthiocholine (0.79 mM, 25°C). It is known that temperature may have a significant effect on enzyme structure dynamics. To test link between BChE structure dynamics and stereoselectivity we performed activity measurements in the absence and presence of ethopropazine at 12, 20, 25, 30 and 37 °C. Our results will give more insight into BChE stereoselectivity with purpose of future drug design especially for chiral drugs or prodrugs.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Farmacija

POVEZANOST RADA