Development of Mass Spectrometry based Analytical Tools for Animal Venoms Characterization

Animal venoms and toxins are now recognized as major sources of bioactive molecules that may be tomorrow’s new drug leads. Their complexity and their potential as drug sources have been demonstrated by application of modern analytical technologies, which have revealed venoms to be vast peptide combinatorial libraries. Structural as well as pharmacological diversity is immense, and mass spectrometry is now one of the major investigative tools for the structural investigation of venom components.
The present work is dedicated to the development of new mass spectrometry-based methodologies for the study of animal venoms. The first methodology depicts an original approach to sequence snake toxins in a higher throughput way after an orthogonal separation of the crude venom. The second analytical development is devoted to decipher disulfide connectivity in cone snails’ toxins through a combination of partial reduction/oxidation followed by ion mobility separation of the semi-reduced/oxidized species and CID fragmentation.
The last part of this work is focused on the capture of ligands of nAChRs in complex mixtures of peptides, especially in cone snail venoms. A new ligand has been discovered and fully characterized.