The self-assembled of cyclic D,L-α- Peptide systems: Insights into the structure and energetics

摘要

Cyclic d,l-α-peptides are able to self-assemble to nanotubes, although the inherent reason of the stability of this kind of nanotube as well as the intrinsic driving force of self-assembly of the cyclic d,l-α-peptides still remain elusive. In this work, using several computational approaches, we investigated the structural and energy characteristics of a series of cyclo[(-l-Phe-d-Ala-)_4] and cyclo[(-l-Ala-d-Ala-)_4] oligomers. The results reveal that the thermodynamic stability, cooperativity, and self-assembly patterns of cyclic d,l-α-peptide nanotubes are mainly determined by the interactions between cross-strand side chains instead of those between backbones. For cyclo[(-l-Phe-d-Ala-)_4] oligomers, the steric interaction between cross-strand side chains, especially the electrostatic repulsion between the phenyls in Phe residues, brings anticooperative effect into parallel stacking mode, which is responsible for the preference of self-assembling nanotube in antiparallel vs. parallel stacking orientation. Based on our results, a novel self-assembling mechanism is put forward-it is the l-l antiparallel dimer of cyclo[(-l-Phe-d-Ala-)_4], instead of the commonly presumed monomer, that acts as the basic building block in self assembly. It explains why these cyclic peptides uniquely self-assemble to form antiparallel nanotubes.