Polymeric protecting groups for peptide and aptamer therapeutics

PMSE 563

Newell R Washburn, washburn@andrew.cmu.edu1, Steve Sun1, Stefani Penn1, and Sidi A Bencherif, sabenche@andrew.cmu.edu2. (1) Departments of Chemistry and Biomedical Engineering, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh, PA 15217, (2) Department of Chemistry, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh, PA 15213
Therapeutics based on peptides or aptamers require protection from endogenous enzymes to increase their lifetime in the circulatory system. Functionalization with poly(ethylene glycol) (PEGylation) has been used extensively but often results in significant decreases in therapeutic activity. There are several water-soluble polymers that are alternatives to PEG, many of which can be synthesized with controlled radical polymerization techniques, which yield materials with narrow polydispersity. Extending work done on synthesizing the adhesion peptide RGD functionalized with poly(hydroxyethyl methacrylate) using atom transfer radical polymerization (ATRP), we demonstrate that therapeutically active peptides and aptamers can be functionalized with water-soluble alternatives to PEG. Examples that were used to test this approach were the GGNECDIARMWEWECFERL peptide, which is a known inhibitor of vascular endothelial growth factor (VEGF), and a DNA aptamer against interleukin-1β that was developed for the purposes of this project. Preliminary work focused on functionalization with poly(hydroxyethyl methacrylate) and measurement of binding affinity as a function of polymer molecular weight.
 

Advances in Protein Drugs and Gene Delivery: Delivery and Diagnostic Technologies
8:30 AM-12:00 PM, Thursday, 14 September 2006 San Francisco Marriott -- Salon 7, Oral

Division of Polymeric Materials: Science & Engineering

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006