Discrimination of Stereoisomers by Their Enantioselective Interactions with Chiral Cholesterol-Containing Membranes

作者：Tsuchiya Hironori^*; Mizogami Maki

来源：Molecules, 2018, 23(1): 49.

DOI：10.3390/molecules23010049

• stereoisomer
• discrimination
• enantioselective membrane interaction
• chiral membrane
• cholesterol

Discrimination between enantiomers is an important subject in medicinal and biological chemistry because they exhibit markedly different bioactivity and toxicity. Although stereoisomers should vary in the mechanistic interactions with chiral targets, their discrimination associated with the mode of action on membrane lipids is scarce. The aim of this study is to reveal whether enantiomers selectively act on chiral lipid membranes. Different classes of stereoisomers were subjected at 5-200 M to reactions with biomimetic phospholipid membranes containing similar to 40 mol % cholesterol to endow the lipid bilayers with chirality and their membrane interactions were comparatively evaluated by measuring fluorescence polarization. All of the tested compounds interacted with cholesterol-containing membranes to modify their physicochemical property with different potencies between enantiomers, correlating to those of their experimental and clinical effects. The rank order of membrane interactivity was reversed by changing cholesterol to C3-epimeric -cholesterol. The same selectivity was also obtained from membranes prepared with 5-cholestan-3-ol and 5-cholestan-3-ol diastereomers. The opposite configuration allows molecules to interact with chiral sterol-containing membranes enantioselectively, and the specific configuration of cholesterol's 3-hydroxyl group is responsible for such selectivity. The enantioselective membrane interaction has medicinal implications for the characterization of the stereostructures with higher bioactivity and lower toxicity.

• 出版日期2018-1