Macromolecule-induced assembly of coiled-coils in alternating multiblock polymers.
The bioconjugation of proteins and peptides with synthetic polymers is a promising method for tailoring the chemical, biological, and physical properties of both the polymeric and protein-based components. Here, we describe macromolecular assemblies of polyethylene glycol-coiled-coil alternating multiblock polymers guided by hetero- and homodimeric association of coiled-coils. High molecular weight, alternating block polymers of polyethylene glycol (PEG) and coiled-coil peptides were formed via facile NHS-activated amide bond formation under strictly anhydrous conditions. Confirmation of multiblock formation was assessed via a combination of NMR spectroscopy, size-exclusion chromatography, and electrophoretic analysis. Formation of the alternating multiblock polymers 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 dichroic spectroscopy and analytical ultracentrifugation, as well as via dynamic and static light scattering. The assembled structures formed in phosphate buffered saline even at very dilute concentrations of multiblock polymer and exhibited controlled sizes relevant in applications such as drug delivery and controlled release.
Sahin
Erinc
E
Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716, USA.
Kiick
Kristi L
KL
D001704:Biopolymers / Q000737:chemistry*; D002850:Chromatography, Gel; D002942:Circular Dichroism; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry*; D014461:Ultracentrifugation
D001704:Biopolymers; D010455:Peptides; D011506:Proteins