DESIGN OF SYNTHETIC BRANCHED-CHAIN POLYPEPTIDES AS CARRIERS FOR BIOACTIVE MOLECULES

New groups of synthetic biodegradable branched chain polypeptides have been prepared with the general formula poly[Lys-(X(i)DL-Ala(m))] [XAK] or poly[Lys-(DL-Ala(m)-X(i))] [AXK], where m similar to 3 and i < 1, and used to elucidate structural and functional properties required for the selection of macromolecular carriers for (i) targeting/delivery of antitumor agents (e.g. daunomycin, methotrexate, boron derivatives), peptide hormones (e.g. GnRH antagonist) or radionuclides for imaging (e.g. I-123, In-111 Cr-51) or therapy (e.g. Sm-153, I-131) or (ii) the construction of synthetic antigens with peptide epitopes of mucin or Herpes Simplex virus glycoprotein D. Principles applicable for a rational carrier design are outlined based on chemical (size, charge, solution conformation) and biological (cytotoxicity, pirogenicity, biodegradation, immunogenicity, immunomodulatory potential, biodistribution) characterization of these biopolymers and their conjugates.