Confinement of folding motifs within central blocks improves single chain polymer nanoparticle folding

Folding polymers into well-defined structures in solution is a critical step towards fully synthetic protein mimics. Peptide motifs such as diphenylalanine (FF) provide a versatile and thermally reversible way to guide the collapse of polymer chains in water, but there have been relatively few studies exploring their use to direct the folding of 'single chain polymer nanoparticles' (SCNPs) to date. Using a recently developed automated synthesis of multiblock peptide-DMA copolymers, we probe the effect that the peptide position and density as well as the overall size of the polymer has on SCNP folding, as measured by GPC and DOSY-NMR. We show that by controlling the position of the peptide within the polymer it is possible to form well-defined SCNPs, with levels of compaction close to globular proteins at relatively low levels of the folding motif. The tunability offered by both the sequence of the peptide and its position within the polymer makes these an excellent class of folding motifs for preparing water soluble and biocompatible SCNPs. Controlling the location of a folding motif within the backbone of a polymer chain can dramatically improve the folding of the polymer into single chain polymer nanoparticles (SCNPs).