Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1974 Feb;71(2):265–268. doi: 10.1073/pnas.71.2.265

Long-Range, pH-Dependent Effects on the Carbon-13 Nuclear Magnetic Resonance Spectra of Oxytocin*

Roxanne Deslauriers †, Roderich Walter ‡, Ian C P Smith †
PMCID: PMC387983  PMID: 4521798

Abstract

The effects of hydrogen ion concentrations on the carbon-13 nuclear magnetic resonance spectra of oxytocin were investigated. The starting pD of 3.0 was increased stepwise to 8.4. A change of the state of protonation of the N-terminal amino group of oxytocin is accompanied by changes in chemical shifts of carbon-13 nuclei of amino-acid residues located in the 20-membered ring of the hormone. The resonance positions of the acyclic peptide portion, Pro-Leu-Gly-NH2, remain constant. The pD-induced chemical-shift changes of carbons up to five bonds removed from the site of protonation are interpreted in terms of “through-bond” and “through-space” mechanisms. Chemical-shift changes of carbons more than five bonds removed are proposed to have a conformational origin. It is suggested that a change in the charge density of the amino group perturbs the dihedral angle of the —CH2—S—S—CH2— moiety of oxytocin, which in turn significantly affects the overall conformation of the 20-membered ring of the hormone.

Keywords: “through-bond” mechanism, “through-space” mechanism, conformation, peptide hormones

Full text

PDF
265

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BRESLOW E. The cupric ion complexes of oxytocin and 2-phenylalanine oxytocin. Biochim Biophys Acta. 1961 Nov 11;53:606–609. doi: 10.1016/0006-3002(61)90230-x. [DOI] [PubMed] [Google Scholar]
  2. Christl M., Roberts J. D. Nuclear magnetic resonance spectroscopy. Carbon-13 chemical shifts of small peptides as a function of pH. J Am Chem Soc. 1972 Jun 28;94(13):4565–4573. doi: 10.1021/ja00768a026. [DOI] [PubMed] [Google Scholar]
  3. Freedman M. H., Lyerla J. R., Jr, Chaiken I. M., Cohen J. S. Carbon-13 nuclear-magnetic-resonance studies on selected amino acids, peptides, and proteins. Eur J Biochem. 1973 Jan 15;32(2):215–226. doi: 10.1111/j.1432-1033.1973.tb02599.x. [DOI] [PubMed] [Google Scholar]
  4. Glickson J. D., Urry D. W., Walter R. Method for correlation of proton magnetic resonance assignments in different solvents: conformational transition of oxytocin and lysine vasopressin from dimethylsulfoxide to water. Proc Natl Acad Sci U S A. 1972 Sep;69(9):2566–2569. doi: 10.1073/pnas.69.9.2566. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Gurd F. R., Lawson P. J., Cochran D. W., Wenkert E. Carbon 13 nuclear magnetic resonance of peptides in the amino-terminal sequence of sperm whale myoglobin. J Biol Chem. 1971 Jun 10;246(11):3725–3730. [PubMed] [Google Scholar]
  6. Hase S., Walter R. Symmetrical disulfide bonds as S-protecting groups and their cleavage by dithiothreitol: synthesis of oxytocin with high biological activity. Int J Pept Protein Res. 1973;5(4):283–288. doi: 10.1111/j.1399-3011.1973.tb03463.x. [DOI] [PubMed] [Google Scholar]
  7. Horsley W. J., Sternlicht H. Carbon-13 magnetic resonance studies of amino acids and peptides. J Am Chem Soc. 1968 Jul 3;90(14):3738–3748. doi: 10.1021/ja01016a025. [DOI] [PubMed] [Google Scholar]
  8. Lyerla J. R., Jr, Barber B. H., Freedman M. H. Carbon-13 chemical shifts accompanying helix formation. Can J Biochem. 1973 Apr;51(4):460–464. doi: 10.1139/o73-053. [DOI] [PubMed] [Google Scholar]
  9. Saitô H., Smith I. C. Carbon-13 nuclear magnetic resonance studies of polyamino acids: the helix-coil transition of poly-L-lysine. Arch Biochem Biophys. 1973 Sep;158(1):154–163. doi: 10.1016/0003-9861(73)90608-5. [DOI] [PubMed] [Google Scholar]
  10. Urry D. W., Walter R. Proposed conformation of oxytocin in solution. Proc Natl Acad Sci U S A. 1971 May;68(5):956–958. doi: 10.1073/pnas.68.5.956. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Walter R., Glickson J. D. Proton magnetic resonance study of peptide conformation: effect of trifluoroethanol on oxytocin and 8-lysine-vasopressin. Proc Natl Acad Sci U S A. 1973 Apr;70(4):1199–1203. doi: 10.1073/pnas.70.4.1199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Walter R., Prasad K. U., Deslauriers R., Smith I. C. Conformational studies of oxytocin, lysine vasopressin, arginine vasopressin, and arginine vasotocin by carbon-13 nuclear magnetic resonance spectroscopy. Proc Natl Acad Sci U S A. 1973 Jul;70(7):2086–2090. doi: 10.1073/pnas.70.7.2086. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Walter R., Schwartz I. L., Darnell J. H., Urry D. W. Relation of the conformation of oxytocin to the biology of neurohypophyseal hormones. Proc Natl Acad Sci U S A. 1971 Jun;68(6):1355–1359. doi: 10.1073/pnas.68.6.1355. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES