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-(Xi-DL-Alam)] or poly[Lys-(DL-Alam-Xi)] [AXK], where m approximately 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. 123I, 111In, 51Cr) or therapy (e.g. 153Sm, 131I) 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.