title: Benzophenone-containing cholesterol surrogates: synthesis and biological evaluation.
abstract: Eight analogs of cholesterol (1) containing a benzophenone group have been synthesized as prospective photoaffinity labels for studies in cellular sterol efflux and HDL formation. Six of these compounds (4-9) have the photophore replacing different portions of the cholesterol alkyl side chain, and two (10 and 11) have it attached via nitrogen at carbon 3. The suitability of these analogs as cholesterol surrogates was determined by examining their ability to replace [3H]1 in fibroblasts preequilibrated with [3H]1. All eight analogs were effective in replacing natural 1 in competition with [3H]1 for apolipoprotein A-I-induced efflux. These are the first compounds shown to replace cholesterol successfully in a complex pathway of multiple intracellular steps. The results suggest an unexpected tolerance of biological membranes regarding the incorporation of sterols of differing chemical structure.
authors.affiliation: Department of Chemistry, Dartmouth College, Hanover, NH 03755, USA. taspen@dartmouth.edu
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Spencer
authors.forename: Pingzhen
authors.initials: P
authors.lastname: Wang
authors.forename: Dansu
authors.initials: D
authors.lastname: Li
authors.forename: Jonathon S
authors.initials: JS
authors.lastname: Russel
authors.forename: David H
authors.initials: DH
authors.lastname: Blank
authors.forename: Jarkko
authors.initials: J
authors.lastname: Huuskonen
authors.forename: Phoebe E
authors.initials: PE
authors.lastname: Fielding
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Fielding
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D001577:Benzophenones / Q000138:chemical synthesis* / Q000378:metabolism; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D005347:Fibroblasts; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism; D014316:Tritium
chemical_list: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D001577:Benzophenones; D012333:RNA, Messenger; D014316:Tritium; D002784:Cholesterol