Hybrid molecular assemblies in combinations of a synthetic peptide lipid with macrocyclic cyclophanes

Abstract

AbstractHybrid molecular assemblies were prepared as combinations of a synthetic lipid, involving an L‐alanine residue interposed between an anionic head group and a hydrophobic double‐chain segment, with macrocyclic hosts, cage‐type cyclophanes having a rigid molecular framework and peptide cyclophanes bearing four flexible branches. Each host was completely incorporated into a relatively polar domain close to the vesicular surface, as confirmed by ultrasensitive differential‐scanning calorimetry and dynamic‐light‐scattering measurements as well as by gel‐filtration chromatography and electronic‐absorption spectroscopy. Perturbation effects of the hosts on the membrane structure were characterized on the basis of steady‐state fluorescence polarization, evaluated using a fluorescent probe, 1‐[4‐(trimethylammonio)phenyl]‐6‐phenyl‐1,3,5‐hexatriene iodide, and thermodynamic parameters associated with the phase transition between gel and liquid‐crystalline states. The cage‐type cyclophanes caused a disturbance of the orderly bilayer lipid membrane in the liquid‐crystalline phase due to their rigid conformational framework, while the peptide cyclophanes generated little effect on the lipid fluidity. The hybrid molecular assembly formed with the lipid and the cage‐type host exercised effective molecular recognition toward α‐amino acids with an aromatic moiety through hydrophobic, π‐π and chirality‐based interactions; L‐ and D‐tryptophan were strongly incorporated into the host cavities as confirmed by 1H‐NMR spectroscopy. On the other hand, the hybrid assembly showed no capacity to bind aliphatic guests, such as L‐methionine and L‐threonine.