Synthesis of a biotin-tagged photoaffinity probe of 2-azetidinone cholesterol absorption inhibitors.
The design and synthesis of a biotin-tagged photoreactive analogue C-4 of the cholesterol absorption inhibitor Ezetimibe is described. Photoaffinity labeling of intestinal brush border membrane vesicles with C-4 and subsequent streptavidin-biotin chromatography leads to selective extraction of a 145 kDa integral membrane protein as the molecular target for cholesterol absorption inhibitors.
Frick
Wendelin
W
Aventis Pharma Deutschland GmbH, Disease Group Metabolic Diseases Industriepark Höchst, Building G 879 D-65926, Frankfurt am Main, Germany.
Bauer-Schäfer
Andrea
A
Bauer
Jochen
J
Girbig
Frank
F
Corsiero
Daniel
D
Heuer
Hubert
H
Kramer
Werner
W
D000818:Animals; D000924:Anticholesteremic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001384:Azetidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001710:Biotin / Q000031:analogs & derivatives* / Q000737:chemistry; D002250:Carbon Radioisotopes; D002784:Cholesterol / Q000378:metabolism; D015195:Drug Design; D000069438:Ezetimibe; D005243:Feces / Q000737:chemistry; D007082:Ileum / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D051379:Mice; D008871:Microvilli / Q000378:metabolism; D019920:Photoaffinity Labels / Q000737:chemistry*; D011817:Rabbits; D051381:Rats
C116379:2-azetidinone; D000924:Anticholesteremic Agents; D001384:Azetidines; D002250:Carbon Radioisotopes; D008565:Membrane Proteins; D019920:Photoaffinity Labels; D001710:Biotin; D002784:Cholesterol; D000069438:Ezetimibe