13C nuclear magnetic resonance studies of the peptide hormones oxytocin, arginine vasopressin, isotocin, mesotocin, glumitocin, aspartocin, related analogues, and diastereoisomers. Use of specifically deuterated hormone derivatives for assignments and effects of structural changes on 13C NMR chemical shifts in peptides

Victor J Hruby, K. K. Deb, Arno F. Spatola, Donald A. Upson, Diane Yamamoto

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Abstract

The 13C nuclear magnetic resonance (NMR) spectra of the naturally occurring peptide hormones oxytocin, arginine vasopressin (AVP), mesotocin, isotocin, aspartocin, and glumitocin were compared. Oxytocin derivatives specifically deuterated in the Half-Cys-1, Tyr-2, Ile-3, Half-Cys-6, Pro-7, or Gly-NH2-9 positions were used to make unequivocal assignments of most of the α and β carbon atoms, and to sort out differences in assignments previously reported. Arginine vasopressin derivatives, specifically deuterated in the Half-Cys-1, Tyr-2, Phe-3, Half-Cys-6, or Gly-N H2-9 positions, also were used for unequivocal assignments. The chemical shifts of invariant residues in these compounds were virtually unchanged from their positions in oxytocin despite the structural changes at positions 8 and/or 4, and differences in biological activities. Analogues with L-amino acid substitutions in the 1 position [(1-penicillaminc]oxytocin), 3 position [(Phe3]oxytocin), 4 position ([Leu4]oxytocin), and 2 and 4 positions ([Leu2,Leu4]oxytocin, [Ile2,Leu4]oxytocin, and [Phe2,Leu4]oxytocin), also generally showed only minor 13C NMR chemical shifts at invariant residues, though there were a few notable exceptions. An interesting observation was that except for the half-cystine residues, the Cα 13C chemical shifts of L-amino acid residues were essentially the same whatever their sequence position in the 20-membered disulfide ring moiety of these peptides. However, there were large 13C chemical shift differences (1.4-1.9 ppm) for the Cα of equivalent L-amino acids in the same molecule, when one residue was in the 20-membered ring moiety, and the other in the acyclic tripeptide moiety of the hormones. The α chemical shift of residues in the acyclic portion of the molecule were always upfield to those in the ring moiety. When D-half-cystine (positions 1 and 6) or D-tyrosine (position 2) were substituted into oxytocin or AVP, the 13C NMR spectra of the diastereoisomeric peptide hormones often showed significant chemical shift perturbations even for residues quite remote from the substitution position. The similarities and differences of 13C chemical shifts are briefly discussed in terms of the conformational and biological properties of these peptides.

Original languageEnglish (US)
Pages (from-to)202-212
Number of pages11
JournalJournal of the American Chemical Society
Volume101
Issue number1
Publication statusPublished - 1979

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ASJC Scopus subject areas

  • Chemistry(all)

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