Conformational studies on [Pro3, Gly4]-oxytocin in dimethyl sulfoxide by 1H nuclear magnetic resonance spectroscopy: evidence for a type II beta turn in the cyclic moiety.

A model for oxytocin has been previously proposed in which residues 3 and 4 occupy the corner positions in a beta turn (Urry, D. W., & Walter, R (1971) Proc. Natl. Acad. Sci. U.S.A. 68, 956). The analogue [Pro(3),Gly(4)]-oxytocin (PGO) was used in proton magnetic resonance (1H NMR) studies designed to probe the contribution of these corner positions in forming a beta turn. Comparison of various 1H NMR parameters obtained at 220 MHz for backbone amide protons of PGO with those for the corresponding protons of oxytocin suggests that, to a first approximation, these two peptides may have similar backbone conformations in )CD3)2SO. Theoretically, the L-Pro lead toGly sequence in positions 3 and 4 of PGO would allow the formation of either a type I or type II beta turn. The two coupling constants between vicinal amide and C alpha protons for Gly(4) of PGO in (CD3)2SO are compatible with a type II beta turn in which 04, the dihedral angle about the bond between the backbone C alpha and N' atoms of Gly4, is appromximately +92 degrees, but not with a type I beta turn. A survey of peptides studied in other laboratories by X-ray and/or 1H NMR with reported type II beta turns with L-Pro lead toGly or Gly lead to Gly sequences in the corner positions revealed a close correlation between chemical shifts and vicinal coupling constants for the glycl residue in the second corner position. It is suggested that this criterion can form an additional basis for the characterization of beta turns. More studies are needed to determine the particular type of beta turn manifest in the cyclic moiety of oxytocin per se, although a reasonable working hypothesis is that oxytocin, similar to PGO, has a type II beta turn.

Conformational studies on arginine vasopressin and arginine vasotocin by proton magnetic resonance spectroscopy.

The assignments and partial conformational analysis of the 220-MHz (1)H nuclear magnetic resonance spectrum of the neurohypophyseal hormones arginine vasopressin and arginine vasotocin in uniformaly deuterated dimethylsulfoxide are reported. The chemical shifts, vicinal coupling constants, temperature coefficients of chemical shifts, and proton-deuterium exchange rates for protons of arginine vasopressin and arginine vasotocin are compared with those for the corresponding protons of the related neurohypophyseal hormones lysine vasopressin and oxytocin. Although to a first approximation the backbone conformations of the hormones exhibit conformational similarities, spectral differences are seen for protons in the amino acid residues that comprise the 20-membered ring moieties. It is inferred that there is a gradual shift in the average conformation in going from arginine vasopressin and lysine vasopressin via arginine vasotocin to oxytocin. As judged on the basis of earlier studies, it is evident that the C-terminal acyclic tail moiety exhibits an enhanced mobility over that of the ring moiety in all of the neurohypophyseal hormones studied and, moreover, that this motion is greater in arginine vasopressin and arginine vasotocin than in oxytocin.