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 halogenati on of tryptophan in peptides recovered from the venom of carnivorous m arine cone snails (Conus). The residue, L-6-bromotryptophan, was ident ified in the sequence of a heptapeptide, isolated from Conus imperiali s, a worm-hunting cone, This peptide does not elicit gross behavioral symptoms when injected centrally or peripherally in mice, L-6-Bromotry ptophan was also identified in a 33-amino acid peptide from Conus radi atus; 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 Pca-Cys-Gly-Gln-Ala-Trp-Cys-NH2 [GRAPHICS] were determined using a combination of mass spectrometry, amino acid, and c hemical sequence analyses, where Pca = pyroglutamic acid, Hyp = hydrox yproline, Gla = gamma-carboxyglutamate, and Trp = L-6-bromotryptophan , The precise structure and stereo chemistry of the modified residue w ere determined as L-6-bromotryptophan by synthesis, co elution, and en zymatic hydrolysis experiments, To our knowledge this is the first doc umentation of tryptophan residues in peptides/proteins being modified in a eukaryotic system and the first report of halogenation of tryptop han in vivo.