cis-parinaric acid is a ligand for the human peroxisome proliferator activated receptor gamma: development of a novel spectrophotometric assay for the discovery of PPARgamma ligands.
Peroxisome proliferator activated receptor gamma (PPARgamma) is the subject of intense investigation as a target for drugs against diabetes, atherosclerosis and cancer. For this reason there is considerable interest in the spectrum of compounds that bind this receptor. In this paper we have identified cis-parinaric acid (CPA) as a novel hPPARgamma ligand. The binding of this fatty acid to the receptor increases its fluorescence and causes a shift in the UV spectrum. This spectral shift is reversible by competition with other known ligands for PPARgamma. This report represents the first direct demonstration of a fatty acid binding to PPARgamma.
Palmer
C N
CN
Biomedical Research Centre and ICRF Molecular Pharmacology Unit, Ninewells Hospital and Medical School, University of Dundee, UK. palmerc@icrf.icnet.uk
Wolf
C R
CR
D001483:Base Sequence; D001667:Binding, Competitive; D018076:DNA, Complementary; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D011485:Protein Binding; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D018076:DNA, Complementary; D005231:Fatty Acids, Unsaturated; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D011994:Recombinant Proteins; D014157:Transcription Factors; C013641:parinaric acid