Application of the Congener Approach to the Design and Synthesis of Peptide-Catecholamine Conjugates

The potential for increasing the therapeutic index of drugs through covalent attachment to natural or synthetic macromolecules was first demonstrated almost 30 years ago.1 Since that time, a wide variety of both drugs and polymeric carriers has been studied in this context.2–4 However, these studies have failed to result in a generalized understanding of the factors which are important for optimization of the design of polymeric drug conjugates. This may be attributable, in part at least, to the fact that the vast majority of carriers studied have been high molecular weight and also polydisperse. Characterization of the polymer-drug conjugates --both chemical and biological --; is therefore difficult. Correlations between the properties of the carrier and the resultant conjugate are often impossible.