Identification of Conotoxins with Novel Odd Number of Cysteine Residues from the Venom of a Marine Predatory Gastropod Conus Leopardus Found in Andaman Sea

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 cysteines.

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.