Stimuli-responsive properties of conjugates of N-isopropylacrylamide-co-acrylic acid oligomers with alanine, glycine and serine mono-, di- and tri-peptides

A random oligomer of N-isopropylacrylamide (NIPAAm) and acrylic acid (AAc) with a AAc content of 3.1 +/- 0.19 mmol carboxylic acid groups per gram of the oligomer and with a number average molecular weight of 1400 was synthesised by a free radical polymerisation using AIBN in DMF. Then, mono-, di-, and tri-peptide conjugates of this oligomer were prepared by using carboxyl-ends-protected (with methyl ester hydrochloride) forms of alanine, glycine and serine, with a water-soluble carbodiimide. 95, 93, and 31%, of the carboxylic acids were conjugated (loaded) at the first step (mono-peptides) with glycine, alanine and serine, respectively. At the second step, percentage of the conjugation of carboxylic acid groups with glycine, alanine and serine were between 99 and 80, 68 and 100, and 21 and 58%, respectively, while the third amino acids were attached to only 21-64% of the carboxylic acids available on the conjugate chains. A decrease was observed in the lower critical solution temperatures (LCSTs) of the amino acid conjugates at pH 4.0 compared with the unconjugated oligomer, which has LCST at 37.7 degreesC at the same pH. LCSTs of di- and tri-peptide conjugates at pH 4.0 were in the range of 38.4-43.3 degreesC, and 42.6-50.8 degreesC, respectively. At pH 7.4, LCSTs of the mono- and di-peptide conjugates were observed in the range of 41.6-43.9 degreesC, and 46.2-60.2 degreesC, respectively, while the co-oligomer at pH 7.4 did not show a LCST up to 60 degreesC. Tri-peptide conjugates did not display LCST at pH 7.4, except the one with glycine-alanine-serine sequence. (C) 2001 Elsevier Science B.V. All rights reserved.