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 synthes ised 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 car boxylic acids were conjugated (loaded) at the first step (mono-peptides) wi th glycine, alanine and serine, respectively. At the second step, percentag e of the conjugation of carboxylic acid groups with glycine, alanine and se rine were between 99 and 80, 68 and 100, and 21 and 58%, respectively, whil e the third amino acids were attached to only 21-64% of the carboxylic acid s available on the conjugate chains. A decrease was observed in the lower c ritical 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 t he 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 ran ge of 41.6-43.9 degreesC, and 46.2-60.2 degreesC, respectively, while the c o-oligomer at pH 7.4 did not show a LCST up to 60 degreesC. Tri-peptide con jugates 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.