Document Detail

A comparison of phosphonothioic acids with phosphonic acids as phosphatase inhibitors.
MedLine Citation:
PMID:  12904075     Owner:  NLM     Status:  MEDLINE    
Phosphorothioates, analogues of phosphate esters in which a sulfur replaces an oxygen atom in the phosphoryl group, are competent surrogate substrates for a number of phosphatases. In some cases the thio analogues show similar binding (as estimated by K(m)) while other phosphatases show quite different K(m) values for phosphate compared to phosphorothioate esters. On this basis it was hypothesized that there might be different inhibitory tendencies by the nonhydrolyzable analogues, phosphonothioic acids compared with phosphonic acids. A series of phosphonothioic acids and corresponding phosphonic acids were synthesized and their inhibitory properties were compared toward human placental and E. coli alkaline phosphatases, the protein-tyrosine phosphatase from Yersinia, and the serine/threonine protein phosphatases PP2C and lambda. Sulfur substitution for oxygen gives the phosphonothioic acids pK(a) values that are close to those of phosphate esters, in contrast to the higher pK(a) values typical of phosphonic acids. Despite different steric requirements and differences in charge distribution in the anions of phosphonothioic acids compared with phosphonic acids, it was found that, with some exceptions, differences in inhibitory properties were modest.
Krzysztof Swierczek; Arti S Pandey; John W Peters; Alvan C Hengge
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  46     ISSN:  0022-2623     ISO Abbreviation:  J. Med. Chem.     Publication Date:  2003 Aug 
Date Detail:
Created Date:  2003-08-07     Completed Date:  2003-09-09     Revised Date:  2013-04-17    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3703-8     Citation Subset:  IM    
Department of Chemistry and Biochemistry, Utah State University, Logan, UT 84322-0300, USA.
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MeSH Terms
Alkaline Phosphatase / antagonists & inhibitors,  chemistry
Enzyme Inhibitors / chemical synthesis*,  chemistry
Escherichia coli / enzymology
Organophosphonates / chemical synthesis,  chemistry
Organophosphorus Compounds / chemical synthesis*,  chemistry
Phosphoprotein Phosphatases / antagonists & inhibitors,  chemistry
Placenta / enzymology
Protein Tyrosine Phosphatases / antagonists & inhibitors,  chemistry
Structure-Activity Relationship
Yersinia / enzymology
Grant Support
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Organophosphonates; 0/Organophosphorus Compounds; EC Phosphatase; EC Phosphatases; EC phosphatase 2C; EC Tyrosine Phosphatases

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