Background: Conotoxins are neuro-pharmacologically active cysteine rich peptides
isolated from the venom complex of marine cone snails. These are usually made of even number of
Method: In this study we characterised six novel conotoxin sequences from the venom of Conus
leopardus collected from the Andaman Sea, namely Le907 (C-C), Le868 (C-C), Le933 (-C-CC),
Le949 (-C-CC), Le1988 (C-C-CC-C) and Le1642 (CC-C-C) using de novo mass spectrometrybased
sequencing methods. Astonishingly 3 of these peptides possess novel arrangements of cysteine
residues with odd number of cysteines (-C-CC; C-C-CC-C), namely Le933, Le949 and
Le1988. Further, a post-translational variant of peptide Le933 was identified and experimentally
determined to contain hydroxyproline.
Results: The unusual cysteine arrangements observed suggests novel class of conotoxins. These
results expand our understanding of the diversity of odd cysteine arrangements in conotoxins.