@unpublished{pittir26730,
           month = {June},
           title = {Modular Supramolecular Biomaterials Based on a Coiled-Coil Scaffold},
          author = {Kaylyn Oshaben},
            year = {2016},
        keywords = {coiled coil, peptide, supramolecular polymer, helix, biomaterial, self assembly},
             url = {http://d-scholarship-dev.library.pitt.edu/26730/},
        abstract = {Nature uses proteins and nucleic acids to form a wide array of structural motifs. Chemists have applied these motifs to the rational design of supramolecular biomaterials. Intricate assemblies of fibers, nets and spheres have been synthesized and characterized; however, existing approaches often lack fine control over size and morphology. In an effort to address this limitation, we have developed a system based on self-assembly of a modular subunit consisting of two {\ensuremath{\alpha}}-helical peptides, which self associate to form a coiled coil, attached at their midpoints by a small organic linking group. 

We found that the linker identity not only impacted the flexibility of the assemblies but linker length was important to maintaining the folding of the peptides in the subunit. Our subunit design also allowed us to examine if assembly size could be controlled by changes to coiled-coil stability through sequence mutations. Supramolecular polymer growth models show assembly size can be controlled by changes in the association affinity of the monomer. We designed, synthesized and characterized a series of coiled coils with varying folded stabilities to use in the subunits and observed that assembly size increased when the stability of the coiled coil is increased.

With the impact of the components of our self-assembling subunits characterized, we began examining if added functionality fluctuated with changes to the subunit. We developed a synthetic scheme for attaching a donor fluorophore and used a capping peptide labeled with an acceptor fluorophore to study F{\"o}rster resonance energy transfer in the dimeric coiled coil and larger assemblies.

Finally, we observed that GCN4-p1, a well studied dimeric coiled coil, crystallized as either a dimer or trimer depending on the crystallization conditions. We carried out an extensive panel of solution-phase experiments to determine if the trimeric oligomerization state exists as measureable population. We found the solution conditions impact the preferred oligomerization state in the GCN4-p1 sequence.}
}