Self-association and solubility of peptides. Solvent-titration study of protected C-terminal segments of porcine secretin.

Self-association of peptides (related to the C-terminal sequence of porcine secretin) in methylene chloride was disrupted by adding dimethylsulfoxide in increasing amounts. This structural transition was monitored by the disappearance of the amide-I C = O stretching band of strongly intermolecularly hydrogen-bonded molecules (1625-1630 cm-1) in the infrared absorption spectra. The effects induced by main-chain length and sequence, type of N alpha-protection, and concentration were assessed. Hexamethylphosphortriamide was compared for its structure-disrupting properties to dimethylsulfoxide. The increasing propensity to aggregate displayed by these peptides is paralleled by a decrease in their solubility. The impact of these results on the planning of peptide syntheses is briefly discussed.