title: Cone snail venomics: from novel biology to novel therapeutics.
abstract: Peptide neurotoxins from cone snails called conotoxins are renowned for their therapeutic potential to treat pain and several neurodegenerative diseases. Inefficient assay-guided discovery methods have been replaced by high-throughput bioassays integrated with advanced MS and next-generation sequencing, ushering in the era of 'venomics'. In this review, we focus on the impact of venomics on the understanding of cone snail biology as well as the application of venomics to accelerate the discovery of new conotoxins. We also discuss the continued importance of medicinal chemistry approaches to optimize conotoxins for clinical use, with a descriptive case study of MrIA featured.
authors.affiliation: Centre for Pain Research, Institute for Molecular Bioscience, University of Queensland, Queensland, Australia.
authors.forename: Jutty Rajan
authors.initials: JR
authors.lastname: Prashanth
authors.forename: Andreas
authors.initials: A
authors.lastname: Brust
authors.forename: Ai-Hua
authors.initials: AH
authors.lastname: Jin
authors.forename: Paul F
authors.initials: PF
authors.lastname: Alewood
authors.forename: Sébastien
authors.initials: S
authors.lastname: Dutertre
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Lewis
mesh_terms: D000818:Animals; D020916:Conotoxins / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D055808:Drug Discovery; D057166:High-Throughput Screening Assays; D008978:Mollusk Venoms / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D009422:Nervous System Diseases / Q000188:drug therapy; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D057786:Peptidomimetics; D012908:Snails / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D020916:Conotoxins; D008978:Mollusk Venoms; D050484:Norepinephrine Plasma Membrane Transport Proteins; D019151:Peptide Library; D010455:Peptides; D057786:Peptidomimetics; C500187:Xen2174