Designing simple polymers with PROTEIN-like ACTIVITY: from Cell Penetrating peptide mimics to resilin-inspired co-continuous networks

Greg Tew
University of Massachusetts
Thursday, November 5, 2015
Duke University Schicano B | 4:30pm

Our primary research aim is to create new materials using a combination of principles, many of which are inspired by biology. We will discuss our newest results in which we have successfully mimicked that biological activity of protein transduction domains like HIV-TAT. The versatility of these synthetic mimics provides the opportunity to discover analogs with superior properties compared to their native sequences. Here we report the first detailed structure-activity relationship of a new PTD family of polymers based on a completely abiotic backbone. The synthetic approach easily allows doubling the density of guanidine functional groups, which increases the transduction efficiency of the sequences. Cellular uptake studies on three different cell lines (HEK 293T, CHO, and Jurkat T cells) confirm that these synthetic analogs are highly efficient novel protein transduction domain mimics (PTDMs), that are more effective than TAT49-57 and nonaarginine (R9) and also highlights the usefulness of polymer chemistry at the chemistry- biology interface. In another topic, phase-separated and self-assembled co-network materials offer a simple route to bicontinuous-like morphologies, which are expected to be highly beneficial for applications such as ion, charge, and oxygen transport. Despite these potential advantages, the systematic definition of co-network structures has not been achieved, largely due to the lack of well-controlled chemistries for their preparation. Here, a thiol-ene end-linking platform enables the systematic investigation of phase-separated poly(ethylene glycol) (PEG) and polystyrene (PS) networks in terms of the molecular weight and relative volume fractions of precursor polymers. The ion conductivity and storage modulus of these materials serve as probes to demonstrate that both phases percolate over a wide range of compositions.