A simple efficient synthesis of [23,24]-(13)C(2)-labeled bile salts as NMR probes of protein-ligand interactions.
The synthesis of [23,24]-(13)C(2)-labeled bile salts is achieved through a steroidal side chain degradation and isotopic regeneration strategy. Three common bile acids were degraded to the corresponding C(22 )aldehyde by an oxidative decarboxylation followed by ozonolysis. The side chain was subsequently regenerated via a Horner-Emmons reaction using an ylide generated from (13)C(2)-labeled bromoacetic acid. These compounds were used as probes of protein-bile salt interactions using two- and three-dimensional NMR techniques.
Tochtrop
Gregory P
GP
Department of Molecular Biology & Pharmacology, Washington University School of Medicine, 63110, St. Louis, MO, USA
DeKoster
Gregory T
GT
Cistola
David P
DP
Covey
Douglas F
DF
D001647:Bile Acids and Salts / Q000138:chemical synthesis* / Q000737:chemistry; D002250:Carbon Radioisotopes; D002352:Carrier Proteins / Q000378:metabolism; D003653:Decarboxylation; D006801:Humans; D006900:Hydroxylation; D006913:Hydroxysteroid Dehydrogenases; D007202:Indicators and Reagents; D007553:Isotope Labeling; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008562:Membrane Glycoproteins; D010126:Ozone / Q000737:chemistry; D011506:Proteins / Q000737:chemistry*; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)
D001647:Bile Acids and Salts; D002250:Carbon Radioisotopes; D002352:Carrier Proteins; D006913:Hydroxysteroid Dehydrogenases; D007202:Indicators and Reagents; D008024:Ligands; D008562:Membrane Glycoproteins; D010126:Ozone; D011506:Proteins; C037643:bile acid binding proteins; C435496:AKR1C2 protein, human; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)