Peptides are promising targets as therapeutics for their high specificity to their targets and low immunogenicity. However, the bioavailability of most peptide therapeutics diminishes <i>in vivo</i> due to inefficiencies in cellular uptake and rapid digestion by endogenous proteases. Here we show that preparing peptides as high-density brush polymers protects them from proteolysis in a tunable fashion. Moreover, if we prepare the peptide to contain a singly Arg or Lys in the parent peptide sequence, the resulting polymers are capable of cellular internalization. Using these strategies, we show that preparing a therapeutic peptide as a high-density brush polymer enables cellular penetration as well as protection from proteolysis. Furthermore, we demonstrate that the therapeutic effect of the peptide has not diminished when preparing the peptide as a high density brush polymer. We believe that preparing peptides as high density brush polymers will increase the bioavailability of many peptide therapeutics that otherwise are not bioavailable.

Graft-through polymerization of complex peptides maintains bioactivity while enabling cellular uptake and protection from proteolysis

251st National Meeting (2016)

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