While a great diversity of peptide-based
supramolecular filaments
have been reported, the impact of an auxiliary segment on the chiral
assembly of peptides remains poorly understood. Herein we report on
the formation of chiral filaments by the self-assembly of a peptide-drug
conjugate containing an aromatic drug camptothecin (CPT) in a computational
study. We find that the chirality of the filament is mediated by the
π–π stacking between CPTs, not only by the well-expected
intermolecular hydrogen bonding between peptide segments. Our simulations
show that π–π stacking of CPTs governs the early
stages of the self-assembly process, while a hydrogen bonding network
starts at a relatively later stage to contribute to the eventual morphology
of the filament. Our results also show the possible presence of water
within the core of the CPT filament. These results provide very useful
guiding principles for the rational design of supramolecular assemblies
of peptide conjugates with aromatic segments