title: A novel post-translational modification involving bromination of tryptophan. Identification of the residue, L-6-bromotryptophan, in peptides from Conus imperialis and Conus radiatus venom.
abstract: We report a novel post-translational modification involving halogenation of tryptophan in peptides recovered from the venom of carnivorous marine cone snails (Conus). The residue, L-6-bromotryptophan, was identified in the sequence of a heptapeptide, isolated from Conus imperialis, a worm-hunting cone. This peptide does not elicit gross behavioral symptoms when injected centrally or peripherally in mice. L-6-Bromotryptophan was also identified in a 33-amino acid peptide from Conus radiatus; this peptide has been shown to induce a sleep-like state in mice of all ages and is referred to as bromosleeper peptide. The sequences of the two peptides and were determined using a combination of mass spectrometry, amino acid, and chemical sequence analyses, where Pca = pyroglutamic acid, Hyp = hydroxyproline, Gla = gamma-carboxyglutamate, and Trp* = L-6-bromotryptophan. The precise structure and stereochemistry of the modified residue were determined as L-6-bromotryptophan by synthesis, co-elution, and enzymatic hydrolysis experiments. To our knowledge this is the first documentation of tryptophan residues in peptides/proteins being modified in a eukaryotic system and the first report of halogenation of tryptophan in vivo.
authors.affiliation: The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, La Jolla, California 92037, USA.
authors.forename: A G
authors.initials: AG
authors.lastname: Craig
authors.forename: E C
authors.initials: EC
authors.lastname: Jimenez
authors.forename: J
authors.initials: J
authors.lastname: Dykert
authors.forename: D B
authors.initials: DB
authors.lastname: Nielsen
authors.forename: J
authors.initials: J
authors.lastname: Gulyas
authors.forename: F C
authors.initials: FC
authors.lastname: Abogadie
authors.forename: J
authors.initials: J
authors.lastname: Porter
authors.forename: J E
authors.initials: JE
authors.lastname: Rivier
authors.forename: L J
authors.initials: LJ
authors.lastname: Cruz
authors.forename: B M
authors.initials: BM
authors.lastname: Olivera
authors.forename: J M
authors.initials: JM
authors.lastname: McIntosh
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001966:Bromine; D002851:Chromatography, High Pressure Liquid; D051379:Mice; D008969:Molecular Sequence Data; D008978:Mollusk Venoms / Q000378:metabolism*; D010452:Peptide Biosynthesis; D011499:Protein Processing, Post-Translational; D012908:Snails; D014364:Tryptophan / Q000378:metabolism*
chemical_list: D008978:Mollusk Venoms; D014364:Tryptophan; D001966:Bromine