Benzophenone-containing cholesterol surrogates: synthesis and biological evaluation.
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.
Spencer
Thomas A
TA
Department of Chemistry, Dartmouth College, Hanover, NH 03755, USA. taspen@dartmouth.edu
Wang
Pingzhen
P
Li
Dansu
D
Russel
Jonathon S
JS
Blank
David H
DH
Huuskonen
Jarkko
J
Fielding
Phoebe E
PE
Fielding
Christopher J
CJ
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
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D001577:Benzophenones; D012333:RNA, Messenger; D014316:Tritium; D002784:Cholesterol