Self‐association and solubility of peptides.

Abstract

Self‐associated species of the protected C‐terminal tetrapeptide segment of porcine vasoactive intestinal peptide and related short sequences in methylene chloride have been disrupted by adding increasing amounts of dimethylsulphoxide. This structural transition has been monitored following the disappearance of the amide I carbonyl stretching band assigned to strongly intermolecularly hydrogen‐bonded molecules (1655–1633 cm‐1) in the infrared absorption spectra. A scale for the propensity of the various peptides to aggregate has been established. Substitution of the asparagine residue by a β‐tert.‐butylaspartic acid residue in the tripeptide drastically reduces the extent of self‐association. The increasing tendency to aggregate shown by these peptides is paralleled by a decrease in their solubility. The impact of these results on the strategy of synthesis of porcine vasoactive intestinal peptide is briefly outlined.