Naslov
Quantum Chemical Investigation of Intermediates in Enzyme Catalyzed Hydrolysis

Autori
Hrenar, Tomica ; Primožič, Ines ; Tomić, S. ; Meić, Z.

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

Izvornik
1st Central European Conference Chemistry towards Biology Portorož / - Portorož, 2002

Skup
1st Central European Conference Chemistry towards Biology Portorož

Mjesto i datum
Portorož, Slovenija, 08.09.2002. - 12.09.2002

Vrsta sudjelovanja
Poster

Vrsta recenzije
Nije recenziran

Ključne riječi
hydrolysis; BChE

Sažetak
Four chiral, quaternary, N-methyl and N-benzyl derivatives of (R)- and (S)-quinuclidin-3-yl benzoates were synthesized and studied as substrates of horse serum butyrylcholinesterase (BChE). The kcat for the substrates decreased in order (R)-N-methyl > (R)-N-benzyl (2-fold slower) >>(S)-N-methyl (70-fold slower reaction), while (S)-N-benzyl ester acts as an inhibitor of the enzyme, KD= 3 mM. The kinetic of inhibition indicated that binding to the catalytic site of BChE occured. The KM values of substrates revealed that the binding affinity of (R)-N-benzyl derivative toward BChE is higher than that of (S)-N-methyl ester. From the ratio of the enantiomeric kcat/KM values, an enantiomeric excess of 95 % was calculated for N-methyl derivatives. Thus, resolution of racemic N-methyl and N-benzyl quinuclidinium esters can be achieved by the hydrolysis catalyzed with BChE. The orientations of all studied benzoate esters in the active site of human BChE have been proposed by flexible ligand docking with AutoDock 3.0 suite of programs.1 The main differences in orientations of obtained Michaelis complexes were found in the ammonium electrostatic region which include interactions of the ammonium moiety of substrates with the indole ring of Trp84 and carboxyl group of Glu199.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

POVEZANOST RADA