Selecting Potential Neuronal Drug Leads from Conotoxins of Various Venomous Marine Cone Snails in Bali, Indonesia

Abstract

Many conotoxins, natural peptides of marine cone snails, have been identified to target neurons. Here, we provide data on pharmacological families of the conotoxins of 11 species of cone snails collected in Bali. The identified definitive pharmacological families possibly targeting neuronal tissues were α (alpha), ι (iota), κ (kappa), and ρ (rho). These classes shall target nicotinic acetylcholine receptors, voltage-gated Na channels, voltage-gated K channels, and α1-adrenoceptors, respectively. The VI/VII-O3 conotoxins might be prospected as an inhibitor of N-methyl-d-aspartate. Con-ikot-ikot could be applied as an α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor blocker medicine. The definitive pharmacology classes of conotoxins as well as those yet to be elucidated need to be further established and verified.

Identification of Novel Conotoxin Precursors from the Cone Snail Conus spurius by High-Throughput RNA Sequencing

“…Sr21.CII01 Con-ikot-ikot precursors with 10 Cyst-residues in the mature toxin that we identified have also been found in other Conus snail species, such as C. geographus [28], C. arenatus [28], and C. victoriae [37]. In our manual Blast search, Sr22.CII02 shared >54 similarity with Con-ikot-ikot precursors of C. praecellens and C. andremenezi [29], which share MTMDMKMTFS residues in the signal peptide. Possibly, Sr22.CII02 precursor is a novel member of the Con-ikot-ikot conopeptides, which then would not be exclusive to Conus fish hunters and that block desensitization of AMPA receptors in dendrites of the mammalian hippocampus [27].…”

“…In C. spurius, we identified two Con-ikot-ikot precursors (Sr21.CII01 and Sr22.CII02): the Sr21.CII01 conopeptide precursor contains a mature toxin with 77 amino acid residues (aa) and 10 Cys residues. Alignment showed 50% identity with the cysteine frameworks of the G005_VD precursor from Conus geographus [28] and ARCII16 precursor from Conus arenatus [29] (Figure 2A). The conopeptide precursor Sr22.CII02 yields a mature toxin with 90 aa residues and eight Cys residues.…”

Synthesis and Characterization of an Analgesic Potential Conotoxin Lv32.1

“…In our work of screening analgesic peptides from the conotoxin libraries established by gene cloning from diverse Conus species, we decoded a peptide sequence of SS C GYLGQH CC IIPKHAY C YGYLE C NNRAV C V from a Conus lividus specimen. This sequence was identical to the mature region of the cDNA-deduced precursor (QGV13653.1) cloned by Mahardika’s group [ 19 ]. We named it Lv32.1 (LvXXXIIA) since it was the first conotoxin with framework XXXII (C-CC-C-C-C) reported from Conus lividus .…”

Diversity of Conopeptides and Conoenzymes from the Venom Duct of the Marine Cone Snail Conus bayani as Determined from Transcriptomic and Proteomic Analyses

“…In total, 82 conotoxin sequences were retrieved from transcriptomic data that contain 54 validated conotoxin sequences clustered into 21 gene superfamilies (O1, O2, M, H, G, P, I1, I2, I3, F, B1, B2, Y, L, A, T, U, S, J, C, and divergent gene family (DGF) [ 28 ]) and 17 others in six other different conotoxin classes (Conkunitzin, Conodipine, Conopressin/Conophysin, Con-ikot-ikot, Conoporin, and Insulin ( Supplementary Table S1 ). In addition, 11 of them were not assigned to any superfamily were given here as UGF (undefined gene family [ 28 ]) M-superfamily accounted for the highest proportion of the known superfamily followed by O1, O2, and DGF ( Figure 2 and Figure 3 ). A total of 12 known cysteine frameworks were also described.…”