The Maynard Group


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Research Overview

Research in the Maynard Group lies at the frontiers of chemistry, biomaterials, and nanotechnology and involves an exciting combination of organic and polymer synthesis, materials characterization, and biomedical research. Below are summaries of some of our current projects on polymer bioconjugates and protein micro and nanoarrays.

Synthetic approaches to protein-polymer conjugates

Protein-polymer conjugates are widely utilized as drugs and are important as reagents in chemical reactions. We develop new synthetic routes to these materials that are efficient and produce fully active conjugates.

Grafting to: To prepare a protein-polymer conjugate, a reactive polymer chain is required. Traditionally, these are made by modifying the chain ends of existing polymers. We synthesize these polymers in one step by using specially designed atom transfer radical polymerization (ATRP) initiators or reversible addition-fragmentation chain transfer (RAFT) polymerization chain transfer agents (CTAs) that react with amino acid side chains.

Grafting from: We also develop new approaches to conjugates where polymers are synthesized by polymerizing directly from proteins, avoiding all polymer-protein coupling reactions. This “grafting from” approach can be accomplished by modifying a protein with an initiator or by preparing amino acids that contain ATRP initiators.

Protein dimers and multimers: In Nature, proteins self assemble into multimers of specific stoichiometry in order to induce biological processes. Thus, conjugate designs that control the number and presentation of proteins should be advantageous to both study these interactions and to prepare therapeutics preorganized into the active state. We target synthetic strategies to generate polymers that are capable of producing homodimers, heterodimers, and star protein conjugates.

Application of bioconjugates in medicine and drug delivery

Controlled radical polymerization strategies are utilized to produce bioactive proteins and siRNA for a variety of targets. Current projects include polymers that stabilize proteins to fluctuations in heat, to long-term storage and to desiccation. These strategies alleviate storage and transport difficulties and facilitate use of both therapeutic and reagent proteins. Similarly, polymers are used to stabilize siRNA to serum and nucleases and provide gene silencing activity in vitro. Peptide-polymer conjugates were readily prepared using polymers with side chains that form oxime bonds so that lengthy protection/deprotection strategies are avoided. Glioblastoma multiforme is a common cancer that has a poor survival prognosis, and peptide-polymers have been employed to synthesize multivalent constructs that preferentially targeted glioblastoma cells. Protein-polymer conjugates are prepared for drug delivery applications. For example, vault-polymer nanocapsules are prepared as smart drug delivery agents for breast cancer.

Polymers and small molecules for biomolecule patterning

We designed end-functionalized small molecules and polymers for efficient conjugation of biomolecules onto surfaces. In all cases, site-selective conjugations are targeted in order to retain biomolecule activity. We synthesize alkane thiols with photo and electrochemical groups for pattern formation on self assembled monolayers (SAMs). Multicomponent patterns are produced by microcontact printing techniques by exploiting dual click reactions on SAMs. Polymers with functionalized end groups are synthesized by ATRP and RAFT polymerization for capture and release of proteins on surfaces.

Multicomponent protein nanopatterns

Many of the desired applications of protein nanoarrays require that multiple different proteins be immobilized in precise locations on a single substrate. We develop strategies to produce both two- and three-dimensional multicomponent nanopatterns using specialty designed polymers and electron beam lithography. Such patterns have tremendous potential to generate surfaces that mimic the complex biological structures found in Nature.

Bioactive surfaces for tissue engineering

Nanoscale chemistry and topography is critical for controlling cell behavior on surfaces. We creat surfaces where cell adhesion ligand presentation and topography are precisely controlled. For example, we fabricated nanoscale features of growth factors important in cell adhesion by patterning a heparin mimicking polymers. We utilize these strategies to enhance endothelial cell adhesion and for stem cell self renewal.