Protein-protein interactions (PPIs) are key interfacial interactions governing many cell signaling pathways. Specifically targeting PPIs is critical as perturbing one upstream interaction can mitigate its downstream effects. However, these complex interactions are difficult to engage as they typically involve many points of contact between interacting proteins, resulting in unique binding motifs for a target. To engage PPIs at the right length scale, in a multivalent fashion, the Gianneschi Lab has developed proteomimetic polymers or protein-like polymers (PLPs) using polymerizable amino acid analogues, incorporated during solid phase peptide synthesis. The tunability of this system allows multiple peptide motifs to be incorporated into a single polymeric structure, which retains bioactivity and resists proteolysis. Thus, PLPs can engage multiple protein binding sites. Peptidyl-olefinic and peptidyl-methacrylic monomers have been synthesized and polymerized via ring opening metathesis polymerization (ROMP) and reversible addition-fragmentation chain-transfer (RAFT), to yield high density, peptide brush polymers in a graft-through approach. The impact of key structural elements, such as polymer backbone architecture and peptide side-chain packing density, on multidomain protein engagement will be presented to develop design rules for these PLPs capable of perturbing PPIs.

Modulating protein-like polymer backbones to recapitulate protein function

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.