Laser Raman Spectroscopy and Circular Dichroism Studies of the Peptide Hormones Mesotocin , Vasotocin , Lysine Vasopressin , and A & nine Vasopressin

Peptide backbone, disulfide bond conformations, and other salient structural features of the naturally occurring neurohypophyseal hormones mesotocin, vasototin, arginine vasopressin, and lysine vasopressin were examined by laser Raman and circular dichroism spectroscopy. Judging from the amide I and III in-plane peptide bond vibrational bands of their Raman spectra, these naturally occurring peptide hormones all have similar peptide backbone conformations. The circular dichroism results also indicate that the gross conformational features of these compounds are similar but further indicate that some increased relative rigidity in the backbone obtains for the vasopressins and at lower pH for all the compounds due to local intramolecular interactions. The conformations about the disulfide bond of all of the native hormones examined are similar, giving a major S-S stretching band at -510 cm-’ in their Raman spectra, and in some cases a minor band at 534 cm-‘. A gauche-gauche-gauche conformation of the C-C-S-S-C-C moiety is possible, but contributions from other conformations are apparent. This is further indicated by the circular dichroism spectra of these compounds which under a variety of conditions show substantial contributions from the disulfide n-u* transition at wavelengths greater than 290 to 300 nm, indicating contributions from conformations of the C-SS-C moiety with dihedral angles ~120” (or less likely ~60”). The intensity of the tyrosine doublet lines at 850 and 830 cm-’ indicate that all four neurohypophyseal hormones examined have their tyrosine aromatic side chain exposed to the outside of the 20-membered ring of the hormone molecule, as was found for oxytocin. The similarities of the conformational properties of the oxytocin-like and vasopressin-like hormones is briefly discussed in terms of their biological and pharmacological activities.