We have designed enzyme-responsive polymer-peptide conjugates based on the amphiphilic block copolymer poly(butadiene-b-ethylene oxide) [PB-PEO].  PB-PEO was functionalized with a peptide designed to facilitate cell-targeting and internalization, which contained a matrix-metalloproteinase (MMP) cleavage site and an integrin binding sequence (RGD).  The MMP-labile peptide sequence was synthesized using solid-phase peptide synthesis, and a carboxyl-functionalized PB-PEO polymer was conjugated to the N-terminus of the peptide on resin.  To investigate the effects of the peptide on the solution-assembly of the PB-PEO-peptide conjugates, a non-peptide containing PB-PEO was synthesized with the same molecular weight and hydrophilic weight fraction as the conjugates.  The non-peptide containing PB-PEO self-assembled into spherical micelles, and the detailed characterization of the PB-PEO-peptide assemblies is ongoing.  Preliminary studies suggest that enzymatic cleavage of the assembled conjugate exposes the RGD sequence, making these PB-PEO-peptide assemblies promising materials for targeted drug delivery.

Synthesis and self-assembly of bio-responsive amphiphilic block copolymers

243rd National Meeting (2012)

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