Foldamer for novel peptide derivatives with pyrene units incorporated into the main chain

A novel foldamer with pyrene units incorporated into a peptide main chain was synthesized and its conformation in solution was investigated by spectroscopic measurements and computational calculations. The foldamer designed here contains 1-aminopyrene-8-carboxylic acid in the sequence, which residue is expected to change the peptide chain direction by 120°. A decapeptide, Boc-Ala-Pyr-Aib-Ala-Aib-Ala-Pyr-Aib-Ala-Aib-OMe, where Boc, Ala, Aib, Pyr, and OMe stand for t-butyloxycarbonyl group, l-alanine, α-aminoisobutyric acid, 1-aminopyrene-8-carboxylic acid, and methyl ester, respectively, was synthesized. Absorption spectroscopy in acetonitrile showed that the two pyrene units in the decapeptide do not interact with each other in the ground state. On the other hand, the fluorescence spectroscopy suggested that the two pyrene units are fixed at a certain distance that allows interaction in the excited state. The circular dichroism spectra showed distinct exciton coupling peaks around the pyrene absorption, further supporting that the two pyrene units have a specific spatial relationship. According to 1H NMR measurements, it was found that the decapeptide has two intramolecular hydrogen bondings and the amide protons of the two 1-aminopyrene-8-carboxylic acid residues are close to each other. The dihedral angles of C-N-Cα-C in the alanine residues were also determined. Taking all these findings into account, molecular mechanics and semiempirical computational calculations were carried out to give two conformations, left-handed and right-handed helices, in which the two pyrene units partially overlap with each other. Theoretical circular dichroism spectra were calculated from these two conformations and compared to the experimental spectrum. It was shown that the left-handed helix conformation is the plausible conformation. The pyrene units incorporated into the main chain are considered to stack with each other by an aromatic interaction, resulting in the formation of a helical structure as a whole.