Abstract

The bioconjugation of proteins and peptides with synthetic polymers is a promising method to tailor chemical, biological and physical properties of both the polymeric and protein-based components. Here, we describe macromolecular assemblies of polyethylene glycol-coiled-coil alternating block copolymers guided by associations of coiled-coils. High molecular weight, alternating block copolymers of PEG and coiled-coil peptides were formed via facile reactions between N-hydroxysuccinimide esters and amines, leading to amide bond formation under anhydrous conditions. Confirmation of multiblock formation was assessed via a combination of NMR spectroscopy, size-exclusion chromatography, and electrophoretic analysis. Formation of the alternating block copolymers of PEG with coiled-coil peptides through the f-position on the heptads did not impair the ability of the coiled-coils to form heterodimers, as assessed via circular dichroic spectroscopy. Interestingly, the conjugation triggered homooligomer formation in one of the peptides that is monomeric in the absence of PEG. The macromolecular assembly of the homooligomer was characterized via circular dichroism, analytical ultracentrifugation, and dynamic and static light scattering. The copolymer structures were formed under physiological conditions, and exhibited controlled sizes relevant in applications such as drug delivery and controlled release.

Our efforts toward synthesis of coiled-coils via recombinant expression have also lead to the discovery of an evolutionary phenomenon. We observed a strong inverse correlation between the pH of an organism’s habitat and its proteomic pI, that is the isoelectric point of bulk of its proteome. This observation may be useful in informed selection of host organisms for recombinant expression of proteins with extreme isoelectric points.