Conopeptidomics of Conus regius

The main objective of this dissertation is the isolation and characterization of novel neuroactive peptides from Conus regius. The conopeptides targeted in this work have a MW of 3500 Da or less, in the hopes that they can become viable drug candidates. A total of 30 sequences were isolated and characterized from the venom of Conus regius, giving us a partial library of the conopeptides found in this species. Techniques such as size exclusion chromatography, reversed phase chromatography, mass spectrometry, nano-nuclear magnetic resonance, chemical modifications of peptides, peptide sequencing through Edman degradation and in some instances bioassays were used together in an effort to perform "conopeptidomics" of Conus regius. The first chapter deals with Conus regius M-superfamily conopeptides. The second chapter is about the A-superfamily conopeptides found in Conus regius. The third chapter deals with Conus regius P-superfamily conopeptides. Finally the fourth chapter encompasses the T-superfamily conopeptides and all other small and linear peptides found in Conus regius that do not have a classification. This work is the first example reported, for any cone snail species, where most of the components of the venom have been sequenced directly for a single cone snail species. This work shows that a more realistic library of conopeptides can be obtained by direct analysis of the venom as opposed to cDNA libraries, which while useful; it does not reflect the post-translational modifications commonly found in conopeptides.