Issue 2, 2016

Activating peptides for cellular uptake via polymerization into high density brushes

Abstract

The utility of peptide therapeutics is thwarted by an inability to enter cells, preventing access to crucial intracellular targets. Herein, we describe a simple and potentially widely applicable solution involving the polymerization of a minimally modified amino acid sequence into a high density brush polymer. Specifically, non-cell penetrating peptides can be rendered competent for cell entry by first including a single Arg or Lys in their amino acid sequence, if one is not already present, along with a norbornenyl unit. This modified monomer is then polymerized by ring opening metathesis polymerization (ROMP). To demonstrate the utility of this strategy, a known therapeutic peptide, which does not penetrate cells on its own, was polymerized. The resulting polymer proficiently entered cells while maintaining its intracellular function. We anticipate that this methodology will find broad use in medicine, increasing or enabling the in vivo efficacy of promising peptide therapeutics.

Graphical abstract: Activating peptides for cellular uptake via polymerization into high density brushes

Supplementary files

Article information

Article type
Edge Article
Submitted
10 Sep 2015
Accepted
19 Oct 2015
First published
10 Nov 2015
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2016,7, 989-994

Author version available

Activating peptides for cellular uptake via polymerization into high density brushes

A. P. Blum, J. K. Kammeyer and N. C. Gianneschi, Chem. Sci., 2016, 7, 989 DOI: 10.1039/C5SC03417E

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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