Synthesis and utilization of 13C and 15N backbone-labeled proline: NMR study of synthesized oxytocin with backbone-labeled C-terminal tripeptide amide

Amino Acids. 2005 Aug;29(2):151-60. doi: 10.1007/s00726-005-0183-z. Epub 2005 Mar 30.

Abstract

The 13C and 15N backbone-labeled proline was prepared using Oppolzer's method based on application of a sultam as chiral auxiliary. This isotopomer was used in the synthesis of the 13C, 15N backbone-labeled C-terminal tripeptide amide fragment of neurohypophyseal hormone oxytocin. Finally, this tripeptide amide was coupled by segment condensation with N-Boc- or N-Fmoc-tocinoic acid, followed by N-deprotection with TFA or piperidine. The labeled oxytocin exhibited biological activity identical with that of natural oxytocin. A detailed 1H, 13C and 15N NMR study confirmed the assigned oxytocin conformation containing a beta-turn in the cyclic part of the molecule, stabilized by H-bond(s) that can be perturbed by the C-terminal tripeptide amide moiety as indicated by comparison of NMR data for both the tocine ring in oxytocin and tocinoic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbon Isotopes
  • Isotope Labeling / methods*
  • MSH Release-Inhibiting Hormone / analogs & derivatives*
  • MSH Release-Inhibiting Hormone / chemical synthesis
  • MSH Release-Inhibiting Hormone / chemistry
  • Nitrogen Isotopes
  • Nuclear Magnetic Resonance, Biomolecular
  • Oxytocin / chemical synthesis*
  • Proline / chemistry*

Substances

  • Carbon Isotopes
  • Nitrogen Isotopes
  • prolyl-leucyl-glycine
  • Oxytocin
  • MSH Release-Inhibiting Hormone
  • Proline