Conformations of isolated fragments of pancreatic polypeptide

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Abstract
In spite of its short polypeptide chain, the pancreatic polypeptide molecule consists of polyproline II type helix and .alpha.-helix. To understand the stability and formation of the .alpha.-helical region, we prepared some peptide fragments including the helical segment of chicken pancreatic polypeptide and studied their conformations by circular dichroism (CD). PP7-36 (a peptide fragment corresponding to residues 7-36 of chicken pancreatic polypeptide) showed a CD spectrum characteristic of the helix at pH 4.6 and at peptide concentrations as low as 1 .mu.M. PP111-36 was able to form a helical conformation only at high peptide concentrations and not at concentrations lower than 10 .mu.M. However, acetyl PP11-36 (in which the .alpha.-amino group is acetylated so that no positive charge exists at the N terminus) was able to form the helical conformation at pH 4.6 and at the peptide concentrations where PP11-36 could not. Succinyl PP12-36 (in which the .alpha.-amino group is succinylated to introduce a negative charge) was also able to form the helical conformation. The CD spectra of PP12-36 and PP13-36 were not characteristic of the helical conformation at all the pH values and peptide concentrations studied. Acetyl PP13-36, which has no charge at the N-terminal end, did form the helix at pH 4.6. These findings indicate that the presence of the negative charge of carboxylate at the N-terminal region of a peptide fragment is important for helix formation. When the carboxyl-terminal amide group of succinyl PP13-36 was converted to a carboxylate group, the resulting peptide was no longer able to form the helix, indicating that the presence of a negative charge at the C terminus of the peptide is unfavorable for helix formation. These observations suggest that the interactions of a negative charge at the N-terminal region and a positive charge at the C-terminal region with the helix dipole are important for stabilizing the helix.