Isolation and characterization of calmodulin-inactivating cholesterol hydroperoxides.
A series of cholesterol hydroperoxides has been prepared and tested as inactivators of calmodulin. Two previously undescribed compounds, tentatively identified as 20-(R)-25-dihydroperoxy-5-cholesten-3 beta-ol and its 20-(S) isomer inactivate calmodulin with 50% loss of activity at 5-10 microM. Cholesterol derivatives with a single hydroperoxy group at C-20 or C-25 are less effective, while 7 alpha-hydroperoxy-cholesterol and 25-hydroxy-cholesterol are inactive. The side-chain hydroperoxide compounds were isolated from a mixture shown earlier to suppress formation of fatty streaks in aortas of rabbits fed a diet supplemented with cholesterol.
Tipton
C L
CL
Department of Biochemistry and Biophysics, Iowa State University, Ames 50011.
Shih
M
M
Magat
W J
WJ
D000818:Animals; D001161:Arteriosclerosis / Q000517:prevention & control; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D006358:Hot Temperature; D009682:Magnetic Resonance Spectroscopy; D010084:Oxidation-Reduction; D011817:Rabbits; D013329:Structure-Activity Relationship
D002147:Calmodulin; C038027:20-hydroperoxycholesterol; C002843:cholesterol hydroperoxide; D002784:Cholesterol