Document Detail

The design, synthesis, and biological evaluation of analogues of the serine-threonine protein phosphatase 1 and 2A selective inhibitor microcystin LA: rational modifications imparting PP1 selectivity.
MedLine Citation:
PMID:  10220039     Owner:  NLM     Status:  MEDLINE    
Based on the results from previously reported molecular modeling analyses of the interactions between the inhibitor microcystin and the serine-threonine protein phosphatases 1 and 2A, we have designed analogues of microcystin LA with structural modifications intended to impart PP1 selectivity. The synthesis of several first generation analogues followed by inhibition assays revealed that all three are PP1-selective, as predicted. Although the observed selectivities are modest, one of the designed analogues is more selective for PP1 than any known small molecule inhibitor.
J B Aggen; J M Humphrey; C M Gauss; H B Huang; A C Nairn; A R Chamberlin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Bioorganic & medicinal chemistry     Volume:  7     ISSN:  0968-0896     ISO Abbreviation:  Bioorg. Med. Chem.     Publication Date:  1999 Mar 
Date Detail:
Created Date:  1999-06-21     Completed Date:  1999-06-21     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  9413298     Medline TA:  Bioorg Med Chem     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  543-64     Citation Subset:  IM    
Department of Chemistry, University of California at Irvine, 92697, USA.
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MeSH Terms
Enzyme Inhibitors / chemical synthesis,  chemistry*,  pharmacology*
Magnetic Resonance Spectroscopy
Mass Spectrometry
Peptides, Cyclic / chemical synthesis,  chemistry*,  pharmacology*
Phosphoprotein Phosphatases / antagonists & inhibitors*,  metabolism
Protein Phosphatase 1
Spectrophotometry, Infrared
Substrate Specificity
Grant Support
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Microcystins; 0/Peptides, Cyclic; 96180-79-9/cyanoginosin-LA; EC Phosphatases; EC Phosphatase 1

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