Polymerization of a peptide-based enzyme substrate

Abstract

Polymers of norbornenyl-modified peptide-based enzyme substrates have been prepared via ring-opening metathesis polymerization (ROMP). Peptides displayed on water-soluble homopolymers retain the ability to be enzymatically processed by a disease-associated enzyme. In contrast, when the peptides are densely arrayed on a nanoparticle derived from a self-assembled amphiphilic block-copolymer, they function with reduced activity as enzymatic substrates.

Fig. 1

A) DLS size intensity distribution of nanoparticles derived from PPA 1 (red), PPA 2 (blue), and PPA 3 (green). (B) TEM of nanoparticles derived from PPA 1. See supporting information for TEM of other NPs.

Fig. 2

RP-HPLC chromatograms of homopolymer prepared from monomer 4 alone (i) as well as following incubation with heat-treated MMP-2 (ii), EDTA-treated MMP-2 (iii), and active MMP-2 (iv). Peak due to peptide-based brush copolymer (*); peak due to peptide cleavage product NH₂-LAGK(Ac)-Ebes-CONH₂ (**).

Scheme 1

Synthesis of peptide-polymer amphiphiles (PPAs) and formulation into nanoparticles. Hydrophobic components of the PPAs are color-coded in red. Hydrophilic components of the PPAs are color-coded with blue.