Targeted Derivatization for a Better MS/MS: Combining Chemistry and an Interactive Search Algorithm for Sequencing Peptides Above 4000 Da

摘要

Spiders are the most successful venomous predators on earth, with more than 42,000 species known - almost half of the species of all venomous animals. These venoms are very complex mixtures of proteinaceous and organic molecules, numbering in the hundreds, which target various receptors, channels and other molecular targets with varying degrees of specificity. This makes venom a very appealing source for potential therapeutics and insecticides. However, the accessibility to these venoms is problematic; most of the spiders are very small, yielding nanoliters of venom and few micrograms of dry protein. This leads to their, and other small venomous animals (such as pseudoscorpions), preclusion from traditional sequencing routes that require copious material. Here we describe the influence of various chemical modifications of the amino acids in the toxins on the coverage obtained by CAD/HCD/ETD fragmentation.