Using Conus venom peptides to understand nervous systems and discover drugs

Abstract

The predatory cone snails have complex venoms; each of the 700 species has 100–200 venom components, mostly small (10–30AA), disulfide‐rich peptides. Conopeptides generally target receptors or ion channels in the nervous system, but there is virtually no molecular overlap between venom components from different Conus species, suggesting over 100,000 peptides in living Conus venoms. Because conopeptides are generally highly specific for a particular molecular target, they have been extensively used to investigate nervous system function, and have therapeutic and other biomedical applications as well. One conopeptide (Prialt) is an approved drug for intractable pain. Each individual peptide can be used as a molecular probe for a specific pharmacological site on a receptor/ion channel complex. The discovery work on Conus peptides has provided a general strategy for the systematic discovery of leads for drugs acting on the nervous system from animal biodiversity. This involves analyzing, in a phylogenetically informed manner, rapidly diversifying gene families (“exogenes”) encoding compounds that act on other animals. Supported by GM48677 from the National Institute of General Medical Science.