title: Cone snail milked venom dynamics--a quantitative study of Conus purpurascens.
abstract: Milked venom from cone snails represent a novel biological resource with a proven track record for drug discovery. To strengthen this correlation, we undertook a chromatographic and mass spectrometric study of individual milked venoms from Conus purpurascens. Milked venoms demonstrate extensive peptide differentiation amongst individual specimens and during captivity. Individual snails were found to lack a consistent set of described conopeptides, but instead demonstrated the ability to change venom expression, composition and post-translational modification incorporation; all variations contribute to an increase in chemical diversity and prey targeting strategies. Quantitative amino acid analysis revealed that milked venom peptides are expressed at ranges up to 3.51-121.01 μM within single milked venom samples. This provides for a 6.37-20,965 fold-excess of toxin to induce apparent IC₅₀ for individual conopeptides identified in this study. Comparative molecular mass analysis of duct venom, milked venom and radula tooth extracts from single C. purpurascens specimens demonstrated a level of peptide continuity. Numerous highly abundant and unique conopeptides remain to be characterized. This study strengthens the notion that approaches in conopeptide drug lead discovery programs will potentially benefit from a greater understanding of the toxinological nature of the milked venoms of Conus.
authors.affiliation: Department of Molecular Biosciences and Bioengineering, College of Tropical Agriculture and Human Resources, University of Hawaii, Honolulu, HI 96822, USA.
authors.forename: Joycelyn B S
authors.initials: JB
authors.lastname: Chun
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Baker
authors.forename: Do H
authors.initials: DH
authors.lastname: Kim
authors.forename: Majdouline
authors.initials: M
authors.lastname: Leroy
authors.forename: Priamo
authors.initials: P
authors.lastname: Toribo
authors.forename: Jon-Paul
authors.initials: JP
authors.lastname: Bingham
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D052078:Conus Snail; D008969:Molecular Sequence Data; D008970:Molecular Weight; D008978:Mollusk Venoms / Q000737:chemistry; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013056:Spectrophotometry, Ultraviolet
chemical_list: D008978:Mollusk Venoms