Peptides displayed as high density brush polymers resist proteolysis and retain bioactivity

Angela P. Blum, Jacquelin K. Kammeyer, Jian Yin, Dustin T. Crystal, Anthony M. Rush, Michael K. Gilson, Nathan C. Gianneschi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

55 Scopus citations


We describe a strategy for rendering peptides resistant to proteolysis by formulating them as high-density brush polymers. The utility of this approach is demonstrated by polymerizing well-established cell-penetrating peptides (CPPs) and showing that the resulting polymers are not only resistant to proteolysis but also maintain their ability to enter cells. The scope of this design concept is explored by studying the proteolytic resistance of brush polymers composed of peptides that are substrates for either thrombin or a metalloprotease. Finally, we demonstrate that the proteolytic susceptibility of peptide brush polymers can be tuned by adjusting the density of the polymer brush and offer in silico models to rationalize this finding. We contend that this strategy offers a plausible method of preparing peptides for in vivo use, where rapid digestion by proteases has traditionally restricted their utility.

Original languageEnglish (US)
Pages (from-to)15422-15437
Number of pages16
JournalJournal of the American Chemical Society
Issue number43
StatePublished - Oct 29 2014

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry
  • Catalysis
  • Colloid and Surface Chemistry


Dive into the research topics of 'Peptides displayed as high density brush polymers resist proteolysis and retain bioactivity'. Together they form a unique fingerprint.

Cite this