Conformation of Lysine Vasopressin: A Comparison with Oxytocin

Abstract

Starting with assignments of proton nuclear magnetic resonance previously made for oxytocin in deuterated dimethylsulfoxide at 220 MHz, we have assigned resonances for the mammalian antidiuretic hormone, lysine vasopressin. The results demonstrate that spectral assignments of neurohypophyseal hormones and their congeners can, within certain limits, be derived from each other. Comparison of the spectra of lysine vasopressin and oxytocin suggests that the gross backbone conformations of their 20-membered ring components are for the most part similar in deuterated dimethylsulfoxide, whereas the C-terminal acyclic amino-acid sequence of lysine vasopressin is more flexible than that of oxytocin.

Method for Correlation of Proton Magnetic Resonance Assignments in Different Solvents: Conformational Transition of Oxytocin and Lysine Vasopressin from Dimethylsulfoxide to Water

“…There is evidence that the conformations of oxytocin (20) and Lys-VP are somewhat different, not only in Me2SO (2,15) but in water as well, as may be deduced from the data summarized in Table 1. In our preferred assignment of peptide NH resonances, there are significant differences among chemical shifts and coupling constants associated with residues at corresponding sequence positions of these two hormones.…”

“…The intense five-proton absorption of the phenylalanine aromatic CH hydrogens, and the characteristic AA'BB' pattern of the tyrosine aromatic CH protons, are readily discerned between 6.5 and 7.5 ppm (1400-1700 Hz). Dispersed among these aromatic resonances, and occurring in the same order as in oxytocin (1), are six single-proton absorptions originating from carboxamide hydrogens assigned previously (2,15 (Figs. 2 and 3).…”

“…It has been reported that the Tyr NH absorption in spectra of oxytocin and Lys-VP broadens when they are recorded in [U-2H]Me2SO (1,2,16 (Fig. 3) (Fig.…”

“…The mole fraction of water was estimated from the relative integrals of H20 and (CH3)2SO resonances. PMR spectra were measured on a Varian Associates HR-220 NMR Spectrometer (2). Chemical shifts were referred to the methyl resonance of the internal standard, sodium 2,2-dimethyl-2-silapentane-5-sulfonate, unless otherwise indicated.…”

Conformational Studies of Oxytocin, Lysine Vasopressin, Arginine Vasopressin, and Arginine Vasotocin by Carbon-13 Nuclear Magnetic Resonance Spectroscopy

“…Conformational analysis of data from proton nuclear magnetic resonance ('H NMR) spectroscopy has contributed significantly to elucidation of the preferred solution conformations of oxytocin (1,2) and lysine vasopressin ([Lys8]VP) (3)(4)(5)(6)(7). Nevertheless, the conformational analysis involves several approximations: (1) the relationship between the dihedral angle 0 (NH-CaH) and the measured three-bond coupling constant 3JHNCH (8,9)-a spectral parameter most useful when considered in combination with potential energy maps (10,11); (2) temperature (12) and solvent (13,14) dependences of chemical shifts and proton exchange rates (15)(16)(17) of peptide hydrogens as related to their solvent-exposed or solvent-shielded state.…”