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.
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.
Craig
A G
AG
The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, La Jolla, California 92037, USA.
Jimenez
E C
EC
Dykert
J
J
Nielsen
D B
DB
Gulyas
J
J
Abogadie
F C
FC
Porter
J
J
Rivier
J E
JE
Cruz
L J
LJ
Olivera
B M
BM
McIntosh
J M
JM
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*
D008978:Mollusk Venoms; D014364:Tryptophan; D001966:Bromine