The Maynard Research Group
Department
of Chemistry and Biochemistry
University of California, Los Angeles
Research
Integrating polymeric materials with biologically-derived molecules in innovative ways is the research focus of the Maynard Group. Polymer complexes with peptides, proteins, and sugars are useful and timely for applications in nanotechnology and medicine. Currently, our efforts are focused on three major areas: protein-polymer conjugates, protein arrays, and polymeric drugs.
Conjugates. Protein-polymer conjugates are important commercial therapeutics and arguably will become valuable building blocks of nanostructured materials. These conjugates are prepared by reacting preformed polymer chains with the protein. We synthesize polymers using initiators that also react with proteins. The result is functional polymers amenable to coupling to proteins without additional reaction or activation steps. For example, we prepared polymers with narrow molecular weight distributions modified at one end with activated disulfides using a pyridyl disulfide-functionalized initiator for atom transfer radical polymerization (Equation 1). Conjugation to proteins such as bovine serum albumin (BSA) is achieved via cysteine residues. We are extending the approach to prepare bioactive polymers and polymers with different end groups. In addition, we also synthesize conjugates by initiating from specific domains on proteins to prepare protein-polymer conjugates in situ. For example, protein-polymer conjugates were prepared by polymerizing from a streptavidin macroinitiator in aqueous solution at room temperature (Scheme 1). We are exploring this approach to make therapeutically useful bioconjugates.
Scheme 1. Streptavidin as a macroinitiator for polymerization.
Protein Micro- and Nanoarrays. We aim to pattern proteins at the micron and nanometer scale that are specifically oriented such that bioactivity is maintained. To this end, we synthesized a poly(methacrylate) with acetal side chains. Exposure of the polymer film to UV radiation through a mask in the presence of a photoacid generator (PAG) results in hydrolysis of the side chains to aldehydes. We demonstrated that streptavidin is micropatterned on the surface with high fidelity to the original mask (Figure 1) and retention of bioactivity. We are currently exploiting the surfaces for use in the detection of cancer markers and as cell adhesion substrates.
Figure 1. Protein patterning. Films consisting of polymer plus PAG were exposed to deep UV through a 1000 mesh nickel TEM grid (a), which was used as a mask. Green fluorescent streptavidin was specifically patterned to locations of UV exposure following incubation with the biotinylated aldehyde-reactive probe (b). Scale bar = 25 µm
Polymeric Drugs.
Universal polymer scaffolds with sequences of orthogonally reactive groups have
been prepared with the over-all objective of providing rapid access to diverse
arrays of block copolymers. Diblock copolymers were synthesized where one block
reacts directly with amine-containing molecules and the other block reacts with
aminooxy-modified compounds only after treatment with acid (shown below). The
step-wise and selective functionalization of the scaffolds rapidly generates new
block copolymers. This approach eliminates the need to make new block copolymers
from monomers each time. We are exploring this is a easy route to make polymeric
drugs.
