(647d) Engineering Mirror Image Peptide Complexes As Dynamic, Biologically Interactive Elements of Polymer Biomaterials

Towards capturing the highly specific, tunable properties of biological systems, we are developing mirror image peptide complexes, or ‘stereocomplexes’, as bio-interactive, transient junctions in synthetic polymer biomaterials. Building on findings that enantiomeric mixtures of stereoregular polymers or peptides exhibit enhanced stability and mechanical properties relative to the individual components, this talk will describe our group’s research on mirror image peptide stereocomplexes as DNA- and coiled coiled peptide-mimetic components of polymer biomaterials. A series of helical peptides, Ac-d-(AAKAA)_nC-NH₂, Ac-l-(AAKAA)_nC-NH₂, and Ac-l-(AAEAA)_nC-NH₂ (n = 3-5), was prepared successfully by microwave-assisted solid-phase peptide synthesis as confirmed by NMR spectroscopy and matrix-assisted laser desorption ionization mass spectrometry. Increasing the length of the peptide increased the stability of the helix as a function of temperature, which correlated to time required for a polymer-peptide conjugate solution, on its own or in mixtures, to form gels. For solutions of the polymer-peptide conjugates, gelation time decreased with peptide length. Solutions of PEG-Ac-l-(AAEAA)_nC-NH₂ conjugates in water at 300 mg/mL gelled after 12, 10, and 3 weeks for n = 3, 4, and 5, respectively. Homochiral blends of oppositely charged 300 mg/mL solutions of PEG-Ac-l-(AAEAA)_nC-NH₂ and PEG-Ac-l-(AAKAA)_nC-NH₂ conjugates (1:1 volume/volume) gelled in 2 weeks, whereas the analogous mixture of mirror image peptide conjugates, i.e., PEG-Ac-l-(AAEAA)_nC-NH₂ and PEG-Ac-d-(AAKAA)_nC-NH₂ required 8 weeks for gelation. These findings contrast previous reports of mirror image peptide complexes showing stronger intermolecular interactions between enantiomeric mixtures relative to the individual components. In part, these results are attributed to the high water solubility of the helical peptides reducing intermolecular interactions; future work will explore peptides with higher hydrophobic content. In addition to helical peptides, β sheet-forming peptides were also prepared. NMR spectroscopy revealed supramolecular interactions between d- and l-KYFIL peptides, with a maximum change of chemical shift observed for 1:1 mixtures, suggesting the preferred stoichiometry of these stereocomplexes. Going forward, we look forward to using peptide stereocomplexation to impart a myriad of biomimetic properties to polymer biomaterials, including self-healing and shear thinning behaviors, useful for 3D printing-based manufacturing processes and targeting biological proteins, among other applications.