ABSTRACT
Each species of cone snail has been reported to produce in excess of 1000 conopeptides, with an estimated 5% overlap in conopeptides found between species. The small molecular size of conopeptides (typically, 5 kDa) and their relative ease of synthesis, structural stability and target specificity make them ideal pharmacological probes. The broadly evolved bioactivity of conopeptides provides a unique source of new research tools and potential therapeutic agents. These predatory animals produce an estimated approximately 100,000 distinct conotoxins many therapeutically interesting molecules remain to be isolated and characterized from the genus Conus. At the moment, only 0.1% of conopeptides have been characterized pharmacologically, yet many have already been identified with clinical potential (Lewis et al., 2012). Over two decades of research on venom peptides derived from cone snails (“conopeptides or conotoxins”) has led to several compounds that have reached human clinical trials, most of them for the treatment of pain. Remarkably, none of the conopeptides in clinical development mediate analgesia through the opioid receptors, underlying the diverse and novel neuropharmacology evolved by Conus snails. The conopeptides studied to-date in animal models, have exhibited antinociceptive, antiepileptic, neuroprotective or cardioprotective activities. Screening results also suggest applications of conotoxins in cancer, neuromuscular and psychiatric disorders. Additional potentially important applications of conotoxin research are the discovery and validation of new therapeutic targets, also defining novel-binding sites on already validated molecular targets. As the structural and functional diversity of conotoxins is being investigated, the Conus venoms continue to surprise with the plethora of neuropharmacological compounds and potential new therapeutics. This review summarizes recent efforts in the discovery of conopeptides, and their preclinical and clinical development.
