A Versatile Approach for the Syntheses of Poly(ester amide)s with Pendant Functional Groups

Poly(ester amide)s (PEAS) are emerging as promising materials for a wide range of biomedical applications due to their potential for both hydrolytic and enzymatic degradation, as well as the ease with which their properties can be tuned by the choice of monomers. The incorporation of pendant functional handles along the PEA backbone has the potential to further expand their applications by allowing the charge and hydrophilicity of the polymers to be altered, and facilitating the conjugation of active molecules such as drugs, targeting groups, and cell signaling molecules. Described here is a simple and versatile strategy based. on orthogonal protecting groups, by which L-lysine and L-aspartic acid can be incorporated into several families of PEAS based on monomers including the diacids succinic and terephthalic acid, the diols 1,4-butanediol and 1,8-octanediol, and the amino acids L-alanine and L-phenylalanine. All polymers were thoroughly characterized by nuclear magnetic resonance spectroscopy, infrared spectroscopy, size exclusion chromatography, thermogravimetric analysis, and differential scanning calorimetry. It was demonstrated that the side chain protecting groups could be readily removed, allowing the pendant amines or carboxylic acids to be functionalized. In particular, the carboxylic acid groups on a polymer containing L-aspartic acid units were converted to N-hydroxysuccinimidyl esters, providing a useful template for further derivatization. (C) 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 3757-3772, 2009