Analysis of BChE stereoselectivity during carbamoylation via transition state modelling (CROSBI ID 587932)
Prilog sa skupa u zborniku | sažetak izlaganja sa skupa | međunarodna recenzija
Podaci o odgovornosti
Šinko, Goran ; Bosak, Anita ; Kovarik, Zrinka
engleski
Analysis of BChE stereoselectivity during carbamoylation via transition state modelling
BChE and related AChE show stereoselectivity in reaction with chiral ligands or esterification compounds as pesticides or carbamates. Chirality is important property especially in drug design due to regulation of target property or minimizing drug side effects. Enantiomers of pharmacological relevant compounds may have different potency or toxic effects. Here we analyse molecular basis of BChE enantioselectivity in carbamoylation. We studied carbamate derivate of following bronhodilatators: terbutalin, methaproterenol and isoproterenol. Carbamate form of terbutaline is known as bambuterol which is used as pro-drug of terbutaline in racemic form. During reaction between BChE and carbamate derivate transition state is formed prior carbamoylation of catalytic serine. We use this conjugate to study interaction between active site residues and chiral carbamate derivate of tested bronhodilatators. Results show similar binding pattern for enantiomers within BChE active site, but interaction between bronhodilatator hydroxyl group, located on asymmetrical carbon atom, and Glu202 near catalytic serine may be the cause of stereoselectivity. Comparison of free energies of carbamoylation between corresponding enantiomers can be related to difference in conjugate stabilisation due to formation of hydrogen bond with Glu202.
enantioselectivity; carbamate derivatives; terbutalin; metaproterenol; isoproterenol
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Podaci o prilogu
180-x.
2012.
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objavljeno
978-953-95551-4-4
Podaci o matičnoj publikaciji
Book of Abstracts of the FEBS3+ Meeting ˝From molecules to life and back˝, Opatija, Hrvatska
Dumić, Jerka ; Kovarik, Zrinka ; Varljen, Jadranka
Rijeka: Hrvatsko Društvo za Biotehnologiju
Podaci o skupu
FEBS3+ Meeting, From molecules and back,
poster
01.01.2012-01.01.2012
Opatija, Hrvatska