Naturally occurring structural analogues of cholesterol were tested as substrates for lecithin:cholesterol acyltransferase and cholesterol oxidase. Minor differences in reactivity were associated with the nature of the 17β substituent of the sterol nucleus. A cholesterol analogue, N-(2-naphthyl)-23,24-dinor-5-cholen-22-amin-3β-ol, was synthesized by reaction of 3β-acetoxy-23,24-dinor-5-cholen-22-oyl chloride with 2-aminonaphthalene followed by reduction of the intermediate amide with LiAlH4. The analogue showed high structural and functional similarity to cholesterol by the following criteria: comparable limiting areas in surface monolayers, precipitability by digitonin, and reactivity as a substrate in the enzymic reaction catalyzed by lecithin:cholesterol acyltransferase. The position of λmax of the fluorescent emission of N-(2-naphthyl)-23,24-dinor-5-cholen-22-amin-3β-ol in a series of solvents and in phosphatidylcholine vesicles indicated that the hydrocarbon region of the phospholipid bilayer is quite polar, comparable to acetonitrile. Cholesterol, 30 mol % in the vesicles, reduced the apparent polarity of the bilayer interior to that of 2,2,4-trimethylpentane. The solvent-sensitive fluorescence properties of N-(2-naphthyl)-23,24-dinor-5-cholen-22-amin-30-ol reveal a previously unrecognized role of cholesterol, i.e., the regulation of the polarity of the hydrocarbon region of membranes.
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