Steroid cyclophanes as artificial receptors embedded in synthetic bilayer membranes: Aggregation behavior and molecular recognition

Two steroid cyclophanes, having individually L-lysine and L-aspartate residues as connector units interposed between a 1,6,20,25-tetraaza[6.1.6.1]paracylophane skeleton and four cholate moieties, were designed and synthesized. The cationic steroid cyclophane, having L-lysine residues, binds anionic and non-ionic guests very efficiently, while it has no capacity to bind a guest with a positive charge in aqueous solution. On the other hand, the anionic steroid cyclophane, bearing L-aspartate residues, shows good binding affinity toward hydrophobic guests in aqueous solution regardless of their charged states. Aggregate morphology of the cationic and anionic peptide lipids, involving an L-alanine residue interposed between a charged head moiety and a hydrophobic double-chain segment, in the sonicated vesicular state was not perturbed significantly upon formation of hybrid assemblies with the steroid cyclophanes in 2.5 mol%. Even though the anionic bilayer vesicle interacts only weakly with anionic guests, the corresponding hybrid assembly formed with the cationic steroid cyclophane is capable of marked molecular recognition of anionic guests, along with shape-sensitive discrimination, through electrostatic and hydrophobic interactions in aqueous solution. In a similar manner, the cationic bilayer membrane alone is incapable of binding a cationic guest. However, the guest-binding ability is not much enhanced in the presence of the anionic steroid cyclophane. Consequently, the cationic steroid cyclophane can act as an efficient cell-surface receptor model for anionic guests while the anionic steroid cyclophane is not a good receptor model when both are embedded in bilayer membranes.