Self-association and solubility of peptides: solvent-titration study of N alpha-protected C-terminal sequences of substance P

Self-association of N^α-protected peptides related to C-terminal sequences of substance P in methylene chloride was disrupted by adding increasing amounts of various polar organic solvents. This process was monitored by the disappearance of the amide I C?O stretching band (1630 cm^?1) of strongly intermolecularly H-bonded molecules in the irabsorption spectra. The effects induced by main-chain length, incorporation at position 9 of a residue promoting folding (α-aminoisobutyric acid), the nature of solvent, and peptide concentration were established. A corollary ¹H-nmr investigation provided detailed information on the NH protons involved in the self-association process as H-bonding donors. The increasing propensity to aggregate exhibited by these peptides is paralleled by a decrease in their solubility. The impact of these results on the synthesis of substance P short sequences is briefly outlined.