Investigating the structural complexity of ancient Australian arthropod venoms

Abstract

Animal venoms consist of a complex variety of bioactive molecules, among which the vast majority are small peptides, referred to as toxins, stabilized by multiple disulfide bonds. These compounds have been an attractive source for the development of novel therapeutic agents and bioinsecticides due to their high degree of potency and selectivity against a wide range of neuronal receptors and ion channels, besides their inherent structural stabilities. However, due to the low-throughput of existing methods, structural characterization of an insignificant number of venom peptides (<50) has been carried out until the present day. Therefore, this project aims the structural characterization of novel peptides from the venom of a spider, isolated in Dr. Mobli laboratory. For this, it is proposed the recombinant production of novel toxins, belonging to one of 25 structurally distinct superfamilies already identified, using methods optimized for disulfide-rich peptides established by the group of Dr. Mobli. Then, structure determination of this toxin labelled with 13C and 15N isotopes will be carried out through high-throughput multidimensional NMR spectroscopy methods. These approaches produce higher-resolution structures, as lower acquisition times of data, compared to the homonuclear NMR approaches more traditionally applied to toxin structure determination. Thus, the outcome of this study will provide much needed structural data in this interesting class of proteins and provide a novel peptide scaffold for development of a new promising generation of therapeutics and/or insecticides. (AU)