The long-term goals of this research are the development of new methods for the modification of the backbone structure of synthetic poly(amino acids), and the development of such backbone-modified poly(amino acids) as biomaterials for a variety of medical applications such as implantable devices, injectable drug carriers, and biocompatible coatings or membranes. The specific aims of this proposal are to synthesize several backbone-modified poly(amino acids), and to investigate some of their physical, chemical, and biological properties. The proposed synthetic approach is based on the polymerization of alpha-L-amino acids via their side chains, resulting in the incorporation of non-amide bonds into the poly(amino acid) backbone. Two different methodologies will be explored: a) Polymerization of trifunctional amino acids by reaction schemes that include the amino acid side chain. In particular, the applicability of derivatives of L-serine for the synthesis of a polyester will be investigated. b) Polymerization of suitably protected dipeptides by reaction schemes that include the peptide side chains. The applicability of this approach for the synthesis of a series of poly(ester amide)- copolymers will be investigated. The resulting backbone-modified poly(amino acids) will be characterized in terms of their physical and chemical properties, followed by a preliminary toxicological assay. The scope of the toxicological assay will be limited an no attempt is planned to establish the suitability of any material for human use within the framework of this proposal. In summary, our studies will lead to generally applicable methods for the structural modification of the backbone of synthetic poly(amino acids), and to a better understanding of the effect of various backbone modifications on the properties of the polymer. In addition, several backbone-modified poly(amino acids) will be charactrized in sufficient detail to evaluate the potential of these materials for medical applications.
NIH ExPorter
NIH ExPorter