CD and NMR Conformational Preferences of Intrinsically Disordered Amphiphilic Peptides: A New Class of Potential Targets in Drug Discovery

Owing to the large panel of biological functions of peptides and their high specificity and potency, the development of peptide-based therapeutic and diagnostic tools has received increased interest. Peptide amphiphiles (PAs) are an emerging class of molecules in which a bioactive peptide is covalently conjugate to a hydrophobic moiety. Due to the coexistence in the molecule of a hydrophilic peptide sequence and a hydrophobic group, PAs are able to selfassemble spontaneously into a variety of nanostructures, such as monolayers, bilayers, and vesicles. In this work we have synthesized predicted by MEDOR disordered peptide sequences3 functionalized by alkyl chains, and connected by ethoxylic-based linker. The structural properties in solution of these new PAs were investigated using CD, NMR and DLS. The presence of the alkyl chains induces not only the self-assembly of these new PAs into supramolecular aggregates but also a gain of structure within the disordered peptide. The design of supramolecular systems, generated by joining a disordered peptide and a lipophilic moiety, could drive the disordered peptide to fold into a stable structure. This structural modification could be a promising route to develop a new class of bio-molecules for processes in which a specific conformational rearrangement is required.