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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
9
|
| pubmed:dateCreated |
1985-10-17
|
| pubmed:abstractText |
Reversible inhibitors for acetylcholinesterase, AcChE, have been studied. Sterically similar alcohols with tetra-substituted uncharged beta groups, (CH3)3SiCH2CH2OH (I), (CH3)3CCH2CH2OH (IA), and CH3S(O2)CH2CH2OH (VII), bind similarly, KI = 3-9 mM, and each binds similarly to its acetate substrate; cationic analogues, (CH3)3N+CH2CH2OH (IB) and (CH3)2S+CH2CH2OH (II), bind similarly to each other, KI = 0.4 mM, similar to Km values of their acetate substrates, and more strongly than the uncharged alcohols by approximately 1.5 kcal/mol. In comparisons of VII with CH3SO2CH3, II with (CH3)3S+, and IB with (CH3)4N+, hydroxyethyl leads to more favorable binding than methyl by approximately 0.8 kcal/mol, despite lower hydrophobicity. Two hydrophobic methyl groups, in comparison of IA with butanol, and two hydrophilic sulfone O atoms, in comparison of VII with 2-(methylthio)ethanol, increase binding similarly, by 1.0 kcal/mol. Conversion of (CH3)3S+ to (CH3)3S+O also improves binding. However, (CH3)3N+O- does not bind to AcChE, and conversion of 1-(dimethylammonio)-4-pentanone and 2-(dimethylammonio)ethyl acetate to their N-oxides, changes of identical to N+H to identical to N+--O-, decreases binding by 1.5 kcal/mol. Although the -COCH3 group in esters with well-binding beta substituents makes essentially no contribution to binding over that of the alcohols, in esters with weakly bound beta substituents, (CH3)2N+(O-), CH3N+H2, CH3S(O), CH3CH2, and CH3S binding is dominated by the ester -COCH3 group, with values of Km approximately 16 mM.
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| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2-(trimethylsilyl)ethanol,
http://linkedlifedata.com/resource/pubmed/chemical/Acetylcholinesterase,
http://linkedlifedata.com/resource/pubmed/chemical/Butanols,
http://linkedlifedata.com/resource/pubmed/chemical/Choline,
http://linkedlifedata.com/resource/pubmed/chemical/Cholinesterase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Dimethyl Sulfoxide,
http://linkedlifedata.com/resource/pubmed/chemical/Ethanol,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfones,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfonium Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Trimethylsilyl Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/dimethyl sulfone,
http://linkedlifedata.com/resource/pubmed/chemical/sulfocholine
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Sep
|
| pubmed:issn |
0022-2623
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
28
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1309-13
|
| pubmed:dateRevised |
2008-11-21
|
| pubmed:meshHeading |
pubmed-meshheading:4032433-Acetylcholinesterase,
pubmed-meshheading:4032433-Binding, Competitive,
pubmed-meshheading:4032433-Butanols,
pubmed-meshheading:4032433-Chemistry, Physical,
pubmed-meshheading:4032433-Choline,
pubmed-meshheading:4032433-Cholinesterase Inhibitors,
pubmed-meshheading:4032433-Dimethyl Sulfoxide,
pubmed-meshheading:4032433-Ethanol,
pubmed-meshheading:4032433-Kinetics,
pubmed-meshheading:4032433-Physicochemical Phenomena,
pubmed-meshheading:4032433-Structure-Activity Relationship,
pubmed-meshheading:4032433-Sulfones,
pubmed-meshheading:4032433-Sulfonium Compounds,
pubmed-meshheading:4032433-Trimethylsilyl Compounds
|
| pubmed:year |
1985
|
| pubmed:articleTitle |
Effects of charge, volume, and surface on binding of inhibitor and substrate moieties to acetylcholinesterase.
|
| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
|