Structural Studies on Polypeptide Hormones

The structures of three polypeptide hormones (glucagon, a 25-residue analogue of adrenocorticotropin, and parathyroid hormone) which contain enough residues to permit organization have been evaluated in aqueous solution by fluorescence and circular dichroism. The effects of pH, temperature, and guanidine on both tyrosyl and tryptophanyl emission have been measured. None of the fluorescence parameters could be interpreted as revealing a structural modification. Glucagon and parathyroid hormone show weak circular dichroic activity near 222 nm, the wave length region of the n 7r transition of the peptide bond in the a helix. However, much stronger dichroic activity occurs in all three hormones near 200 nm, the region where the random form of the peptide bond is optically active. Although glucagon appears to be almost completely unorganized in aqueous solution, it is a-helical when crystalline. The structure of this polypeptide of 29 amino acid residues appears to undergo a helix to coil transition between its crystalline and aqueous states.