• Fischer rat;
  • opioid peptide;
  • post-translational modification;
  • tryptophan modification


The biotransformation of the opioid peptide dynorphin A(1–17) was investigated in striatum of freely moving Fischer rats, by direct infusion of this peptide, followed by recovery of the resulting biotransformation products via microdialysis and identification using matrix-assisted laser desorption/ionization mass spectrometry. The observed peptides are consistent with enzymatic cleavage at the Arg7-Ile8 position of dynorphin A(1–17), followed by terminal degradation of the resulting dynorphin A(1–7) and dynorphin A(8–17) peptides. Unexpectedly, novel post-translational modifications were found on C-terminal fragments of dynorphin A(1–17). Using tandem mass spectrometry, a covalent modification of mass 172 Da, the nature of which is not understood, was found on the tryptophan residue of C-terminal fragments (Trp14). Additional modifications, of mass 42 and 113 Da, were also found on the N-terminus (Ile8 or Pro10) of these same C-terminal fragments. The role of these modifications of C-terminal fragments has not yet been characterized.