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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
1999-10-28
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pubmed:abstractText |
Rhizopus delemar lipase catalysed ester hydrolysis of the alpha-methoxy-beta-phenylpropanoate 1 affords the (R)-(+) and (S)-(-) isomers in > 84% enantiomeric excess. Absolute stereochemistry was determined by a single crystal X-ray analysis of a related synthetic analogue. The activity of these two enantiomers on glucose transport in vitro and as anti-diabetic agents in vivo is reported and their unexpected equivalence attributed to an enzyme-mediated stereospecific isomerisation of the (R)-(+) isomer. Binding studies using recombinant human PPARgamma (peroxisomal proliferator activated receptor gamma), now established as a molecular target for this compound class, indicate a 20-fold higher binding affinity for the (S) antipode relative to the (R) antipode.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0968-0896
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pubmed:author |
pubmed-author:AllenGG,
pubmed-author:BirrellH CHC,
pubmed-author:BuckleD RDR,
pubmed-author:CantelloB CBC,
pubmed-author:EgglestonD SDS,
pubmed-author:HaighDD,
pubmed-author:HaltiwangerR CRC,
pubmed-author:HolderJ CJC,
pubmed-author:ListerC ACA,
pubmed-author:PintoI LIL,
pubmed-author:RamiH KHK,
pubmed-author:SimsJ BJB,
pubmed-author:SmithS ASA,
pubmed-author:SweeneyJ DJD
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pubmed:issnType |
Print
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pubmed:volume |
7
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
821-30
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pubmed:dateRevised |
2004-11-17
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pubmed:meshHeading |
pubmed-meshheading:10400335-Animals,
pubmed-meshheading:10400335-Crystallography, X-Ray,
pubmed-meshheading:10400335-Hypoglycemic Agents,
pubmed-meshheading:10400335-Models, Chemical,
pubmed-meshheading:10400335-Models, Molecular,
pubmed-meshheading:10400335-Phenylpropionates,
pubmed-meshheading:10400335-Rats,
pubmed-meshheading:10400335-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:10400335-Stereoisomerism,
pubmed-meshheading:10400335-Time Factors,
pubmed-meshheading:10400335-Transcription Factors
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pubmed:year |
1999
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pubmed:articleTitle |
Non-thiazolidinedione antihyperglycaemic agents. Part 3: The effects of stereochemistry on the potency of alpha-methoxy-beta-phenylpropanoic acids.
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pubmed:affiliation |
SmithKline Beecham Pharmaceuticals, New Frontiers Science Park North, Harlow, Essex, UK. david_haigh-1@sbphrd.com
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pubmed:publicationType |
Journal Article
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