Cholesterol is a key steroidal, lipid biomolecule found abundantly in plasma membranes of eukaryotic cells. It is an important structural component of cellular membranes and regulates membrane fluidity and permeability. Cholesterol is also essential for normal functioning of key proteins including ion-channels, G protein-coupled receptors (GPCRs), membrane bound steroid receptors, and receptor kinases. It is thought that cholesterol exerts its actions via specific binding to chiral proteins and lipids as well as through non-specific physiochemical interactions. Distinguishing between the specific and the non-specific interactions can be difficult. Although much remains unclear, progress has been made in recent years by utilizing ent-cholesterol, the enantiomer of natural cholesterol (nat-cholesterol) as a probe. Ent-Cholesterol is the non-superimposable mirror image of nat-cholesterol and exhibits identical physiochemical properties as nat-cholesterol. Hence, if the biological effects of cholesterol result solely due to membrane effects, it is expected that there will be no difference between ent-cholesterol and nat-cholesterol. However, when direct binding with chiral proteins and lipids is involved, the enantiomer is expected to potentially elicit significantly different, measurable effects due to formation of diastereomeric complexes. In this chapter, we have reviewed the literature related to ent-cholesterol and its use as a probe for various biophysical and biological interactions of cholesterol.
Keywords: Cholesterol; Enantiomer; Stereospecificity; Sterol–membrane interactions; Synthesis; ent-Cholesterol.