Research
Overview
Research in the Maynard Group lies at the frontiers of chemistry, biomaterials, biotechnology, and nanotechnology. The work involves an exciting combination of organic and polymer synthesis, materials characterization and biomedical application. Currently the group is applying our polymers to therapeutic delivery of proteins to treat important diseases such as diabetes and cancer. In addition, a part of the group is working on developing new strategies to rapidly and chemoselectively conjugate small molecules and polymers to therapeutic peptides and proteins. As a result, Maynard group members make important contributions to a variety of fields and learn a combination of skills that sets them apart favorably in the job market.
Next Generation Therapeutics and Protein Delivery
Protein therapeutics are an important component of the pharmaceutical market, and protein-polymer conjugates are attractive due to their longer half-lives. We develop new synthetic methods to prepare protein-polymer conjugates. In addition we design polymers that stabilize proteins, both added as excipients and conjugated to proteins. For example, we synthesize trehalose polymers that enhance therapeutic protein pharmacokinetics and storage stabilities. Some of the polymers we synthesize are degradable.
Other Selected Publications
Mancini, R. J.; Lee, J.; Maynard, H. D., “Trehalose Glycopolymers for Stabilization of Protein Conjugates to Environmental Stressors,” J. Am. Chem. Soc., 2012, 134, 8474-8479.
Nguyen, T. H.; Kim, S.-H.; Decker, C. G.; Wong, D. Y.; Loo, J. A.; Maynard, H. D., “A Heparin-Mimicking Polymer Conjugate Stabilizes Basic Fibroblast Growth Factor,” Nature Chemistry, 2013, 5, 221-227.
Lee, J.; Lin, E.-W.; Lau, U. Y.; Hedrick, J. L.; Bat, E.; Maynard, H. D., “Trehalose Glycopolymers as Excipients for Protein Stabilization,” Biomacromolecules, 2013, 14, 2561-2569.
Lin, E. W.; Maynard, H. D., “Grafting from Small Interfering Ribonucleic Acid (siRNA) as an Alternative Synthesis Route to siRNA-Polymer Conjugates,” Macromolecules, 2015, 48, 5640-5647.
Decker, C. G.; Wang, Y.; Paluck, S. J.; Shen, L.; Loo, J. A.; Levine, A. J. Miller L. S.; Maynard, H. D., “Fibroblast Growth Factor 2 Dimer with Superagonist In Vitro Activity Improves Granulation Tissue Formation During Wound Healing,” Biomaterials, 2016, 81, 157-168.
Pelegri-O’Day, E. M.; Bhattacharya, A.; Theopold, N.; Ko, J. H.; Maynard, H. D. “Synthesis of Zwitterionic and Trehalose Polymers for Variable Degradation Rates and Stabilization of Insulin,” Biomacromolecules, 2020, in press.
Responsive Nanomedicines
Stimuli-responsive materials exhibit changes in one or more properties in response to an external trigger. We have developed materials including hydrogels and nanoparticles that respond to a variety of chemical or physical triggers for drug delivery. We apply these materials to proteins that are therapeutics for diabetes and cancer.
Other Selected Publications
Grover, G. N.; Lam, J.; Nguyen, T. H.; Segura, T.; Maynard, H. D., “Biocompatible Hydrogels by Oxime Click Chemistry,” Biomacromolecules, 2012, 13, 3013-3017.
Matsumoto, N. M.; Prabhakaran, P.; Rome, L. H.; Maynard, H. D., “Smart Vaults: Thermally-Responsive Protein Nanocapsules,” ACS Nano, 2013, 7, 867-874.
Matsumoto, N. M.; Buchman, G. W.; Rome, L. H.; Maynard, H. D., “Dual pH- and Temperature-Responsive Protein Nanoparticles,” European Polymer Journal, 2015, 69, 532-539.
Boehnke, N.; Cam, C.; Bat, E.; Segura, T.; Maynard, H. D., “Imine Hydrogels with Tunable Degradability for Tissue Engineering,” Biomacromolecules, 2015, 16, 2101-2108.
Boehnke, N.; Maynard, H. D. “Design of Modular Dual-Enzyme Responsive Peptides,” Peptide Science, 2017, 108 (5), 1-6.
Pelegri-O’Day, E. M.; Matsumoto, N. M.; Tamshen, K.; Raferty, E. D.; Lau, U. Y.; Maynard, H. D. “PEG Analogs Synthesized by Ring-Opening Metathesis Polymerization for Reversible Bioconjugation,” Bioconjugate Chem., 2018, 29, 3739-3745.
Novel Conjugation Methodologies
Current methods to conjugate proteins to other molecules often employ reversible strategies that limit their efficiency and therapeutic effect. To this end, we are developing new strategies to rapidly and chemoselectively conjugate small molecules and polymers to therapeutic peptides and proteins.
