Conotoxin TVIIA, a novel peptide from the venom of Conus tulipa

A novel conotoxin belonging to the ‘four‐loop’ structural class has been isolated from the venom of the piscivorous cone snail Conus tulipa . It was identified using a chemical‐directed strategy based largely on mass spectrometric techniques. The new toxin, conotoxin TVIIA, consists of 30 amino‐acid residues and contains three disulfide bonds. The amino‐acid sequence was determined by Edman analysis as SCSGRDSRCOOVCCMGLMCSRGKCVSIYGE where O = 4‐ trans l ‐hydroxyproline. Two under‐hydroxylated analogues, [Pro10]TVIIA and [Pro10,11]TVIIA, were also identified in the venom of C. tulipa . The sequences of TVIIA and [Pro10]TVIIA were further verified by chemical synthesis and coelution studies with native material. Conotoxin TVIIA has a six cysteine/four‐loop structural framework common to many peptides from Conus venoms including the ω‐, δ‐ and κ‐conotoxins. However, TVIIA displays little sequence homology with these well‐characterized pharmacological classes of peptides, but displays striking sequence homology with conotoxin GS, a peptide from Conus geographus that blocks skeletal muscle sodium channels. These new toxins and GS share several biochemical features and represent a distinct subgroup of the four‐loop conotoxins.