Document Detail


Inhibition of acetylcholinesterase by chromophore-linked fluorophosphonates.
MedLine Citation:
PMID:  20034789     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Fluorophosphonate (FP) head groups were tethered to a variety of chromophores (C) via a triazole group and tested as FPC inhibitors of recombinant mouse (rMoAChE) and electric eel (EEAChE) acetylcholinesterase. The inhibitors showed bimolecular inhibition constants (k(i)) ranging from 0.3 x 10(5)M(-1)min(-1) to 10.4 x 10(5)M(-1)min(-1). When tested against rMoAChE, the dansyl FPC was 12.5-fold more potent than the corresponding inhibitor bearing a Texas Red as chromophore, whereas the Lissamine and dabsyl chromophores led to better anti-EEAChE inhibitors. Most inhibitors were equal or better inhibitors of rMoAChE than EEAChE. 3-Azidopropyl fluorophosphonate, which served as one of the FP head groups, showed excellent inhibitory potency against both AChE's ( congruent with 1 x 10(7)M(-1)min(-1)) indicating, in general, that addition of the chromophore reduced the overall anti-AChE activity. Covalent attachment of the dabsyl-FPC analog to rMoAChE was demonstrated using size exclusion chromatography and spectroscopic analysis, and visualized using molecular modeling.
Authors:
Lilu Guo; Alirica I Suarez; Michael R Braden; John M Gerdes; Charles M Thompson
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural     Date:  2009-12-04
Journal Detail:
Title:  Bioorganic & medicinal chemistry letters     Volume:  20     ISSN:  1464-3405     ISO Abbreviation:  Bioorg. Med. Chem. Lett.     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-02-03     Completed Date:  2010-09-20     Revised Date:  2014-09-24    
Medline Journal Info:
Nlm Unique ID:  9107377     Medline TA:  Bioorg Med Chem Lett     Country:  England    
Other Details:
Languages:  eng     Pagination:  1194-7     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2009 Elsevier Ltd. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Acetylcholinesterase / metabolism*
Animals
Arachidonic Acids / chemistry*,  metabolism,  pharmacology
Cholinesterase Inhibitors / chemistry*,  metabolism,  pharmacology
Mice
Organophosphonates / chemistry*,  metabolism,  pharmacology
Polyethylene Glycols / chemistry,  metabolism,  pharmacology
Grant Support
ID/Acronym/Agency:
P20-RR015583/RR/NCRR NIH HHS; P30 NS055022/NS/NINDS NIH HHS; P30 NS055022-02/NS/NINDS NIH HHS; R43 ES016392/ES/NIEHS NIH HHS; R43 ES017567/ES/NIEHS NIH HHS; R43 ES017567-01A1/ES/NIEHS NIH HHS; U01 ES016102/ES/NIEHS NIH HHS; U01 ES016102-03/ES/NIEHS NIH HHS; U01 ES016102-04/ES/NIEHS NIH HHS; U44 NS058229/NS/NINDS NIH HHS; UO1-ES016102/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Arachidonic Acids; 0/Cholinesterase Inhibitors; 0/Organophosphonates; 0/Polyethylene Glycols; 0/methyl arachidonylfluorophosphonate; 9004-76-6/glycofurol; EC 3.1.1.7/Acetylcholinesterase
Comments/Corrections

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