Stereostructure Dependence Phenomenon on the Self-Assembly of Ala-Ala-Ala Lipotripeptides

A series of lipotripeptide stereoisomers based on alanine were synthesized, and their self-assembling behaviors were studied by means of circular dichroism spectra, ATR-IR, temperature-dependent ¹H NMR, and X-ray diffraction patterns. In the mixed solvent of hexafluoroisopropanol/H₂O (1/9, v/v), eight lipotripeptides were able to self-assembled into nanoflakes or nanoribbons driven by the hydrophobic association of alkyl chains, intermolecular hydrogen bonding among carboxyl groups at C-terminal and amide groups of alanine moieties in the peptide segment. It was found that the stacking chirality of carbonyl groups was determined by the chirality of alanine residue at C-terminal (i.e., "C-terminal determination" rule). Moreover, our research also highlighted the intermolecular hydrogen bonding on amide groups of each alanine residue, terminal carboxyl as well as the molecular packing structures can be subtly manipulated by changing the stereochemical sequence of peptide segment.