Protein-Like Polymers
Professor Nathan Gianneschi (Northwestern University, Department of Chemistry)
Host: Professor Matthew Becker
Tuesday, February 11, 2020 - 11:40am to 1:10pm
Location: French Family Science Center 2237
Rosenthal, Janet

Link for Professor Gianneschi

Abstract:  In this presentation, we will describe the organization of functional peptides as sidechains on polymer scaffolds as a new class of poly(peptide). We categorize these into two general classes; 1) Peptide-Polymer Amphiphiles (PPAs), which consist of block copolymers with a dense grouping of peptides arrayed as the sidechains of the hydrophilic block and connected to a hydrophobic block that drives micelle assembly, and 2) Protein-Like Polymers (PLPs), wherein peptide-brush polymers are composed from monomers, each containing a peptide side-chain. Peptides organized in this manner imbue polymers or polymeric nanoparticles with a range of functional qualities inherent to their specific sequence. Therefore, polymers or nanoparticles otherwise lacking bioactivity, or responsiveness to stimuli, once linked to a peptide of choice, can now bind proteins, enter cells and tissues, have controlled and switchable biodistribution patterns, and be enzyme substrates (e.g. for kinases, phosphatases, proteases). Indeed, where peptide substrates are incorporated, kinetically- or thermodynamically-driven morphological transitions can be enzymatically induced in the polymeric material. Synergistically, the polymer enforces changes in peptide activity and function by virtue of packing and constraining the peptide. The scaffold can protect the peptide from proteolysis, change the pharmacokinetic profile of an intravenously injected peptide, increase the cellular uptake of an otherwise cell impermeable therapeutic peptide, or change peptide substrate activity entirely. Moreover, in addition to the sequence-controlled peptides (generated by solid phase synthesis) the polymer can carry its own sequence-dependent information, especially through living polymerization strategies allowing well-defined blocks and terminal labels (dyes, contrast agents, charged moieties). Hence, the two elements, peptide and polymer, cooperate to yield materials with unique function and properties quite apart from each alone. Herein, we describe the development of synthetic strategies for accessing these classes of biomolecule polymer conjugates, and discuss their utility in a range of settings, including as a new class of peptide therapeutics.