A sleep-inducing peptide from the venom of the Indian cone snail Conus araneosus. (1st September 2015) - Franklin, Jayaseelan Benjamin
Abstract: The marine snail Conus araneosus has unusual significance due to its confined distribution to coastal regions of southeast India and Sri Lanka. Due to its relative scarceness, this species has been poorly studied. In this work, we characterized the venom of C. araneosus to identify new venom peptides. We identified 14 novel compounds. We determined amino acid sequences from chemically-modified and unmodified crude venom using liquid chromatography–electrospray ionization mass spectrometry and matrix assisted laser desorption ionization time-of-flight mass spectrometry. Ten sequences showed six Cys residues arranged in a pattern that is most commonly associated with the M-superfamily of conotoxins. Four other sequences had four Cys residues in a pattern that is most commonly associated with the T-superfamily of conotoxins. The post-translationally modified residue (pyroglutamate) was determined at the N-terminus of two sequences, ar3h and ar3i respectively. In addition, two sequences, ar3g and ar3h were C-terminally amidated. At a dose of 2 nmol, peptide ar3j elicited sleep when injected intraperitoneally into mice. To our knowledge, this is the first report of a peptide from a molluscivorous cone snail with sleep-inducing effects in mice. The novel peptides characterized herein extend the repertoire of unique peptides derived from cone snails and may add value to the therapeutic promise of conotoxins. Graphical abstract: Highlights: We characterized peptides from the venom of Conus araneosus using de novo mass spectrometric techniques. We determined 14 novel amino acid sequences of venom peptides from C. araneosus. Three peptides namely ar3g, ar3h and ar3i contain post-translationally modified residues. This is the first study that demonstrates sleep-inducing activity of a peptide ar3j in mice from a molluscivorous cone snail.