Functional Biomaterials: Tunable Multiblock Hybrid Copolymers as Protein Mimetics

We have created polymer/peptide multiblock hybrid copolymers containing multiple repeats of functional peptides derived from the natural proteins as protein mimetics for biomedical applications. For example, elastin mimetic hybrid polymers (EMHPs) composed of poly(ethylene glycol) (PEG) alternating with an alanine–rich, lysine–containing peptide [(AKA3KA)2, AK2], with or without the cell–binding domains, were synthesized by condensation polymerization employing copper (I) catalyzed alyne–azide cycloaddition (CuAAC) reaction. Covalent crosslinking of [PEG–AK2]n through the lysine amines afforded cell–adhesive, elastomeric hydrogels. Separately, EMHPs consisting of poly(acrylic acid) (PAA) alternating with a elastin–based peptide [(VPGVG)2, VG2] have also been successfully synthesized under CuAAC conditions. [PAA–VG2]n self–assembled into discrete nanoparticles through the concerted interactions between the constituent building blocks. Recently, ultrahigh molecular weight multiblock hybrid copolymers were synthesized employing tetrazine ligation, an ultrafast cycloaddition of s–tetrazine (Tz) with trans–cyclooctene (TCO) derivatives. The modular approaches allow facile substitution of the polymer and peptide segments to fine–tune the materials properties for applications in tissue engineering and drug delivery.

Collaborators:

• Kristi Kiick, Department of Materials Science and Engineering, University of Delaware
• Joseph M. Fox, Department of Chemistry and Biochemistry, University of Delaware

Selected Publications:

1. Han, Z.; Trout, W. S.; Liu, S.; Andrade, G. A.; Hudson, D. A.; Scinto, S. L.; Dicker, K. T.; Li, Y.; Lazouski, N.; Rosenthal, J.; Thorpe, C; Jia, X.; Fox, J. M.* "Rapid Bioorthogonal Chemistry Turn–on through Enzymatic or Long Wavelength Photocatalytic Activation of Tetrazine Ligation", J. Am. Chem. Soc., 2016, 38, 5978–5983.
2. Liu, S.; Zhang, H; Remy R. A.; Deng, F.; Mackay, M. E.; Fox, J. M.*; Jia, X.* "Meter–Long Multiblock Copolymer Microfibers via Interfacial Bioorthogonal Polymerization" Adv Mater, 2015, 27, 2783–2790.
3. Grieshaber, S. E.; Paik, B. A.; Bai, S.; Kiick, K. L.; Jia, X.* "Nanoparticle Formation from Hybrid, Multiblock Copolymers of Poly(acrylic acid) and a VPGVG Peptide" Soft Matter, 2012, 9, 1589–1599.
4. Grieshaber, S. E.; Farran, A. J. E.; Bai, S.; Kiick, K. L.*; Jia, X.* "Tuning the Properties of Elastin Mimetic Hybrid Copolymers via a Modular Polymerization Method" Biomacromolecules, 2012, 13, 1774–1786.
5. Grieshaber, S. E.; Farran, A. J. E.; Lin–Gibson, S.; Kiick, K. L.*; Jia, X.* "Synthesis and Characterization of Elastin–Mimetic Hybrid Polymers with Multiblock, Alternating Molecular Architecture and Elastomeric Properties" Macromolecules, 2009, 42, 2532–2541.