title: Tuning assembly size in Peptide-based supramolecular polymers by modulation of subunit association affinity.
abstract: Nature uses proteins and nucleic acids to form a wide array of functional architectures, and scientists have found inspiration from these structures in the rational design of synthetic biomaterials. We have recently shown that a modular subunit consisting of two α-helical coiled coil peptides attached at their midpoints by an organic linking group can spontaneously self-assemble in aqueous solution to form a soluble supramolecular polymer. Here we explore the use of coiled-coil association affinity, readily tuned by amino acid sequence, as a means to predictably alter properties of these supramolecular assemblies. A series of dimeric coiled-coil peptide sequences with identical quaternary folded structures but systematically altered folded stability were designed and biophysically characterized. The sequences were cross-linked to generate a series of branched, self-assembling biomacromolecular subunits. A clear relationship is observed between coiled-coil association affinity and apparent hydrodynamic diameter of the supramolecular polymers formed by these subunits. Our results provide a family of soluble supramolecular polymers of tunable size and well-characterized coiled-coil sequences that add to the library of building blocks available for use in the rational design of protein-based supramolecular biomaterials.
authors.affiliation: Department of Chemistry, University of Pittsburgh , Pittsburgh, Pennsylvania 15260, United States.
authors.forename: Kaylyn M
authors.initials: KM
authors.lastname: Oshaben
authors.forename: W Seth
authors.initials: WS
authors.lastname: Horne
mesh_terms: D000595:Amino Acid Sequence; D050976:Basic-Leucine Zipper Transcription Factors / Q000737:chemistry / Q000235:genetics; D002942:Circular Dichroism; D003432:Cross-Linking Reagents / Q000737:chemistry; D018360:Crystallography, X-Ray; D008969:Molecular Sequence Data; D009154:Mutation; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D011108:Polymers / Q000138:chemical synthesis* / Q000737:chemistry; D017510:Protein Folding; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics; D013816:Thermodynamics
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D003432:Cross-Linking Reagents; C501391:GCN4 protein, S cerevisiae; D010455:Peptides; D011108:Polymers; D029701:Saccharomyces cerevisiae Proteins