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

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...

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Autores principales: Tsuchiya, Hironori, Mizogami, Maki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5943951/
https://www.ncbi.nlm.nih.gov/pubmed/29295605
http://dx.doi.org/10.3390/molecules23010049
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author Tsuchiya, Hironori
Mizogami, Maki
author_facet Tsuchiya, Hironori
Mizogami, Maki
author_sort Tsuchiya, Hironori
collection PubMed
description 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 μM to reactions with biomimetic phospholipid membranes containing ~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 α-cholesterol. The same selectivity was also obtained from membranes prepared with 5α-cholestan-3β-ol and 5β-cholestan-3α-ol diastereomers. The opposite configuration allows molecules to interact with chiral sterol-containing membranes enantioselectively, and the specific β 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.
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spelling pubmed-59439512018-11-13 Discrimination of Stereoisomers by Their Enantioselective Interactions with Chiral Cholesterol-Containing Membranes Tsuchiya, Hironori Mizogami, Maki Molecules Article 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 μM to reactions with biomimetic phospholipid membranes containing ~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 α-cholesterol. The same selectivity was also obtained from membranes prepared with 5α-cholestan-3β-ol and 5β-cholestan-3α-ol diastereomers. The opposite configuration allows molecules to interact with chiral sterol-containing membranes enantioselectively, and the specific β 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. MDPI 2017-12-25 /pmc/articles/PMC5943951/ /pubmed/29295605 http://dx.doi.org/10.3390/molecules23010049 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tsuchiya, Hironori
Mizogami, Maki
Discrimination of Stereoisomers by Their Enantioselective Interactions with Chiral Cholesterol-Containing Membranes
title Discrimination of Stereoisomers by Their Enantioselective Interactions with Chiral Cholesterol-Containing Membranes
title_full Discrimination of Stereoisomers by Their Enantioselective Interactions with Chiral Cholesterol-Containing Membranes
title_fullStr Discrimination of Stereoisomers by Their Enantioselective Interactions with Chiral Cholesterol-Containing Membranes
title_full_unstemmed Discrimination of Stereoisomers by Their Enantioselective Interactions with Chiral Cholesterol-Containing Membranes
title_short Discrimination of Stereoisomers by Their Enantioselective Interactions with Chiral Cholesterol-Containing Membranes
title_sort discrimination of stereoisomers by their enantioselective interactions with chiral cholesterol-containing membranes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5943951/
https://www.ncbi.nlm.nih.gov/pubmed/29295605
http://dx.doi.org/10.3390/molecules23010049
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