Mass Spec Sequences Venom Peptides

A new mass spectrometry strategy makes it easier to sequence venom peptides, a diverse set of disulfide-rich natural products that are difficult to characterize. For example, the approximately 500 species of cone snails produce more than 50,000 peptide toxins. But researchers have characterized only a fraction of those peptides, which block ion channels and have potential as drugs. No cone snail genomes have been sequenced, so the peptides must be sequenced from scratch without the guidance of DNA databases. Brian T. Chait of Rockefeller University and coworkers sequence cone snail venom peptides by combining electron transfer dissociation (ETD), a type of mass spectrometric fragmentation technique, with chemical derivatization of cysteines to form dimethylated lysine analogs (Proc. Natl. Acad. Sci. USA, DOI: 10.1073/pnas.0900745106). Such derivatization increases the charge state of the peptides and improves the peptide sequence coverage because ETD works better with ions that have higher charge states. Using this strategy, the researchers obtained full sequences for 31 peptide toxins with only 7% of the crude venom from a single cone snail.