2002
DOI: 10.1002/ejoc.200390032
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Stereoselective Hydrolysis of Quaternary Quinuclidinium Benzoates Catalyzed by Butyrylcholinesterase

Abstract: 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 k cat for the substrates decreased in the order (R)-N-methyl Ͼ (R)-N-benzyl (2.3-fold slower) ϾϾ (S)-Nmethyl (70.5-fold slower reaction), while for the (S)-N-benzyl ester inhibition of the enzyme was observed. The kinetics of inhibition (K a = 3.3 µM) indicated that binding to the catalytic site of BChE occurred. From th… Show more

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Cited by 11 publications
(11 citation statements)
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“…The additional favourable interactions of two aromatic parts of 3-S may be the reason for the best inhibitory power of this compound. These results supported our previous findings based on experimental data and quantum-chemical calculations 11,12 that (S)-enantiomers compared to (R)-have stronger interactions within the active site of BChE which successfully compete with productive binding leading to the tetrahedral intermediate and subsequent hydrolysis.…”
Section: Resultssupporting
confidence: 91%
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“…The additional favourable interactions of two aromatic parts of 3-S may be the reason for the best inhibitory power of this compound. These results supported our previous findings based on experimental data and quantum-chemical calculations 11,12 that (S)-enantiomers compared to (R)-have stronger interactions within the active site of BChE which successfully compete with productive binding leading to the tetrahedral intermediate and subsequent hydrolysis.…”
Section: Resultssupporting
confidence: 91%
“…7,8 In our previous work, 9,10 chiral esters of quinuclidin-3-ol and benzoylcholine were subjected to enzymatic hydrolysis in the presence of BChE 11,12 and the kinetics of BChE-catalyzed hydrolyses were determined. The hydrolysis of quaternary quinuclidine esters proved to be highly enantioselective.…”
Section: Introductionmentioning
confidence: 99%
“…K i and k i values for the racemic inhibitor are about the average of those of both enantiomers (Table 2). However, this stereopreference (S < R) is opposite to those reported for the BChE-catalyzed hydrolysis enantiomers of quinuclidin-3-acetate 50 , bambuterol 51 , quinuclidinium benzoate 52 , and cocaine 53 . Modeling both enantiomers of endo-2-norbornyl-N-n-butylcarbamate into the active site of the X-ray structure of BChE 4,5 ( Figure 1) suggests that the norbornyl ring of (S)-enantiomer fits better into the AS of the enzyme than (R)-enantiomer ( Figure 5B).…”
Section: Bche Inhibitions By (R)-(+)-and (S)-(-)-endo-2-norbornyl-n-ncontrasting
confidence: 79%
“…This stereopreference (R < S) is the same as those reported for the BChE-catalyzed hydrolysis enantiomers of (Table 2). quinuclidin-3-acetate 50 , bambuterol 51 , quinuclidinium benzoate 52 , and cocaine 53 . Modeling both enantiomers of exo-2-norbornyl-N-n-butylcarbamate into the active site of BChE 4,5 ( Figure 1) indicates that the norbornyl ring of (R)-enantiomer fits better into the AS of the enzyme than that of (S)-enantiomer ( Figure 5A).…”
Section: Bche Inhibitions By (R)-(+)-and (S)-(-)-exo-2-norbornyl-n-n-mentioning
confidence: 99%
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