Conjugates of Poly(N-isopropyl acrylamide-co-acrylic acid) with alanine monopeptide, dipeptide, and tripeptide

A random copolymer of N-isopropyl acrylamide (NIPAAm) and acrylic acid (AAc) with an AAc content of 3.1 +/- 0.19 mmol of carboxylic acid groups per gram of the copolymer and with a number-average molecular weight of 1400 was synthesized by free-radical polymerization with 2,2'-azoisobutyronitrile in dimethylformamide. Then, monopeptide, dipeptide, and tripeptide (i.e., alanine) conjugates of this copolymer were prepared with their carboxyl-end-protected (with methyl ester hydrochloride) form of alanine, with a water-soluble carbodiimide. Of the carboxylic acids, 93, 69, and 57% were conjugated (loaded) with alanine at the monopeptide, dipeptide, and tripeptide conjugation steps, respectively. The chemical structures of the copolymer and conjugates were analyzed by Fourier transform infrared and H-1-NMR, which revealed the conjugate formation. Amino acid conjugation caused significant decreases in the lower critical solution temperatures (LCST) of the copolymer, especially at pH 7.4. The LCST values of the dipeptide and tripeptide conjugates of poly(NIPAAm-co-AAc) at both pH 4.0 and 7.4 shifted to significantly higher temperatures. (C) 2003 Wiley Periodicals, Inc.