PEGylation affects the self-assembling behaviour of amphiphilic octapeptides

Surfactant-like peptides are a class of amphiphilic macromolecules, which are able to self-assemble in water forming different supramolecular structures. Among them, octapeptides composed of six hydrophobic and two hydrophilic residues have attracted interest since they have a length similar to those of natural phospholipids. Supramolecular structures of different amphiphilic octapeptides have been widely reported, but no study has been performed aimed at investigating the effect of PEGylation on their self-assembling behaviour. The aim of the present work was to synthesize and characterise the self-assembling behaviour of PEGylated alanine- or valine based amphiphilic octapeptides (mPEG_1.9kDa-DDAAAAAA and mPEG_1.9kDa-DDVVVVVV) in comparison to the non-PEGylated ones (DDAAAAAA and DDVVVVVV). The self-aggregation process in ultrapure water was investigated by fluorescence spectroscopy, small angle neutron scattering (SANS), dynamic light scattering (DLS), while the secondary structure was assessed by circular dichroism. PEGylation markedly affects the self-assembling behaviour of these amphiphilic octapeptides in terms of both critical aggregation concentration (CAC) and shape of the formed supramolecular aggregates. Indeed, PEGylation increases CAC and prevents the self-aggregation into fibrillary supramolecular aggregates (as observed for non-PEGylated peptides), by promoting the formation of micelle-like structures (as demonstrated for valine-based octapeptide). On the other side, the secondary structure of peptides seems not to be affected by PEGylation. Overall, these results suggest that self-assembling behaviour of amphiphilic octapeptides can be modified by PEGylation, with a great potential impact for the future applications of these nanomaterials.