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Venomics: a new paradigm for natural products-based drug discovery

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Abstract

The remarkable potency and pharmacological diversity of animal venoms has made them an increasingly valuable source of lead molecules for drug and insecticide discovery. Nevertheless, most of the chemical diversity encoded within these venoms remains uncharacterized, despite decades of research, in part because of the small quantities of venom available. However, recent advances in the miniaturization of bioassays and improvements in the sensitivity of mass spectrometry and NMR spectroscopy have allowed unprecedented access to the molecular diversity of animal venoms. Here, we discuss these technological developments in the context of establishing a high-throughput pipeline for venoms-based drug discovery.

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References

  • Anangi R, Chen C-Y, Cheng C-H, Chen Y-C, Chen C-C, Chu Y-P, Chang C-H, Jeng W-Y, Shiu J-H, Chuang W-J (2007) Expression of snake venom toxins in Pichia pastoris. Toxin Rev 26:169–187

    Article  CAS  Google Scholar 

  • Baell JB, Duggan PJ, Lok YP (2004) ω-Conotoxins and approaches to their nonpeptide mimetics. Aust J Chem 57:179–185

    Article  CAS  Google Scholar 

  • Bahrami A, Assadi AH, Markley JL, Eghbalnia HR (2009) Probabilistic interaction network of evidence algorithm and its application to complete labeling of peak lists from protein NMR spectroscopy. PLoS Comput Biol 5:e1000307

    Google Scholar 

  • Bennett PB, Guthrie HR (2003) Trends in ion channel drug discovery: advances in screening technologies. Trends Biotechnol 21:563–569

    Article  CAS  PubMed  Google Scholar 

  • Biass D, Dutertre S, Gerbault A, Menou JL, Offord R, Favreau P, Stöcklin R (2009) Comparative proteomic study of the venom of the piscivorous cone snail Conus consors. J Proteomics 72:210–218

    Article  CAS  PubMed  Google Scholar 

  • Butler MS (2004) The role of natural product chemistry in drug discovery. J Nat Prod 67:2141–2153

    Article  CAS  PubMed  Google Scholar 

  • Calvete JJ, Juarez P, Sanz L (2007) Snake venomics: strategy and applications. J Mass Spectrom 42:1405–1414

    Article  CAS  PubMed  Google Scholar 

  • Calvete JJ, Sanz L, Angulo Y, Lomonte B, Gutierrez JM (2009) Venoms, venomics, antivenomics. FEBS Lett 583:1736–1743

    Article  CAS  PubMed  Google Scholar 

  • Chen CY, Cheng CH, Chen YC, Lee JC, Chou SH, Huang W, Chuang WJ (2006) Preparation of amino-acid-type selective isotope labeling of protein expressed in Pichia pastoris. Proteins 62:279–287

    Article  CAS  PubMed  Google Scholar 

  • Chen J, Zhang Y, Rong M, Zhao L, Jiang L, Zhang D, Wang M, Xiao Y, Liang S (2009) Expression and characterization of jingzhaotoxin-34, a novel neurotoxin from the venom of the tarantula Chilobrachys jingzhao. Peptides 30:1042–1048

    Article  CAS  PubMed  Google Scholar 

  • Clardy J, Walsh C (2004) Lessons from natural molecules. Nature 432:829–837

    Article  CAS  PubMed  Google Scholar 

  • Cregg JM (2007) Introduction: distinctions between Pichia pastoris and other expression systems. Methods Mol Biol 389:1–10

    Article  CAS  PubMed  Google Scholar 

  • Cregg JM, Cereghino JL, Shi J, Higgins DR (2000) Recombinant protein expression in Pichia pastoris. Mol Biotechnol 16:23–52

    Article  CAS  PubMed  Google Scholar 

  • Cushman DW, Ondetti MA (1991) History of the design of captopril and related inhibitors of angiotensin converting enzyme. Hypertension 17:589–592

    CAS  PubMed  Google Scholar 

  • D’Suze G, Schwartz EF, Garcia-Gomez BI, Sevcik C, Possani LD (2009) Molecular cloning and nucleotide sequence analysis of genes from a cDNA library of the scorpion Tityus discrepans. Biochimie 91:1010–1019

    Article  PubMed  CAS  Google Scholar 

  • Daly R, Hearn MT (2005) Expression of heterologous proteins in Pichia pastoris: a useful experimental tool in protein engineering and production. J Mol Recognit 18:119–138

    Article  CAS  PubMed  Google Scholar 

  • Davis J, Jones A, Lewis RJ (2009) Remarkable inter- and intra-species complexity of conotoxins revealed by LC/MS. Peptides 30:1222–1227

    Article  CAS  PubMed  Google Scholar 

  • Dawson PE, Muir TW, Clark-Lewis I, Kent SBH (1994) Synthesis by native chemical ligation. Science 266:776–779

    Article  CAS  PubMed  Google Scholar 

  • Demain AL, Vaishnav P (2009) Production of recombinant proteins by microbes and higher organisms. Biotechnol Adv 27:297–306

    Article  CAS  PubMed  Google Scholar 

  • Denyer J, Worley J, Cox B, Allenby G, Banks M (1998) HTS approaches to voltage-gated ion channel drug discovery. Drug Discov Today 3:323–332

    Article  CAS  Google Scholar 

  • Ding K, Gronenborn AM (2002) Novel 2D triple resonance NMR experiments for sequential resonance assignments of proteins. J Magn Reson 156:262–268

    Article  CAS  PubMed  Google Scholar 

  • Ducancel F, Boulain JC, Trémeau O, Ménez A (1989) Direct expression in E. coli of a functionally active protein A—snake toxin fusion protein. Protein Eng 3:139–143

    Article  CAS  PubMed  Google Scholar 

  • Dunlop J, Bowlby M, Peri R, Vasilyev D, Arias R (2008) High-throughput electrophysiology: an emerging paradigm for ion-channel screening and physiology. Nat Rev Drug Discov 7:358–368

    Article  CAS  PubMed  Google Scholar 

  • Edwards L, Hessinger DA (2000) Portuguese Man-of-war (Physalia physalis) venom induces calcium influx into cells by permeabilizing plasma membranes. Toxicon 38:1015–1028

    Article  CAS  PubMed  Google Scholar 

  • Eghbalnia HR, Bahrami A, Tonelli M, Hallenga K, Markley JL (2005) High-resolution iterative frequency identification for NMR as a general strategy for multidimensional data collection. J Am Chem Soc 127:12528–12536

    Article  CAS  PubMed  Google Scholar 

  • Escoubas P, King GF (2009) Venomics as a drug discovery platform. Expert Rev Proteomics 6:221–224

    Article  CAS  PubMed  Google Scholar 

  • Escoubas P, Bernard C, Lambeau G, Lazdunski M, Darbon H (2003) Recombinant production and solution structure of PcTx1, the specific peptide inhibitor of ASIC1a proton-gated cation channels. Protein Sci 12:1332–1343

    Article  CAS  PubMed  Google Scholar 

  • Escoubas P, Sollod BL, King GF (2006) Venom landscapes: mining the complexity of spider venoms via a combined cDNA and mass spectrometric approach. Toxicon 47:650–663

    Article  CAS  PubMed  Google Scholar 

  • Escoubas P, Quinton L, Nicholson GM (2008) Venomics: unravelling the complexity of animal venoms with mass spectrometry. J Mass Spectrom Rev 43:279–295

    Article  CAS  Google Scholar 

  • Fiordalisi JJ, James PL, Zhang Y, Grant GA (1996) Facile production of native-like κ-bungarotoxin in yeast: an enhanced system for the production of a neuronal nicotinic acetylcholine receptor probe. Toxicon 34:213–224

    Article  CAS  PubMed  Google Scholar 

  • Francischetti IM, My-Pham V, Harrison J, Garfield MK, Ribeiro JM (2004) Bitis gabonica (Gaboon viper) snake venom gland: toward a catalog for the full-length transcripts (cDNA) and proteins. Gene 337:55–69

    Article  CAS  PubMed  Google Scholar 

  • Frohman MA (1993) Rapid amplification of complementary DNA ends for generation of full-length complementary DNAs: thermal RACE. Methods Enzymol 218:340–356

    Article  CAS  PubMed  Google Scholar 

  • Froy O, Zilberberg N, Gordon D, Turkov M, Gilles N, Stankiewicz M, Pelhate M, Loret E, Oren DA, Shaanan B, Gurevitz M (1999) The putative bioactive surface of insect-selective scorpion excitatory neurotoxins. J Biol Chem 274:5769–5776

    Article  CAS  PubMed  Google Scholar 

  • Fry BG, Roelants K, Champagne DE, Scheib H, Tyndall JD, King GF, Nevalainen TJ, Norman JA, Lewis RJ, Norton RS, Renjifo C, de la Vega RC (2009) The toxicogenomic multiverse: convergent recruitment of proteins into animal venoms. Annu Rev Genomics Hum Genet 10:483–511

    Article  CAS  PubMed  Google Scholar 

  • Fukuyama Y, Iwamoto S, Tanaka K (2006) Rapid sequencing and disulfide mapping of peptides containing disulfide bonds by using 1, 5-diaminonaphthalene as a reductive matrix. J Mass Spectrom 41:191–201

    Article  CAS  PubMed  Google Scholar 

  • Glickman JF, Wu X, Mercuri R, Illy C, Bowen BR, He Y, Sills M (2002) A comparison of AlphaScreen, TR-FRET, and TRF as assay methods for FXR nuclear receptors. J Biomol Screen 7:3–10

    Article  CAS  PubMed  Google Scholar 

  • Güntert P (2004) Automated NMR structure calculation with CYANA. Methods Mol Biol 278:353–378

    PubMed  Google Scholar 

  • Guo RT, Chou LJ, Chen YC, Chen CY, Pari K, Jen CJ, Lo SJ, Huang SL, Lee CY, Chang TW, Chaung WJ (2001) Expression in Pichia pastoris and characterization by circular dichroism and NMR of rhodostomin. Proteins 43:499–508

    Article  CAS  PubMed  Google Scholar 

  • Hamelin M, Meng X, Cuddy M, Korsun K, Ondeyka J, Simpson PB, Cully DF, Priest BT (2005) A high-throughput assay for modulators of ligand-gated chloride channels. Assay Drug Dev Technol 3:59–64

    Article  CAS  PubMed  Google Scholar 

  • Harvey AL (1995) From venoms to toxins to drugs. Chem Ind 22:914–916

    Google Scholar 

  • Herrmann T, Güntert P, Wüthrich K (2002) Protein NMR structure determination with automated NOE assignment using the new software CANDID and the torsion angle dynamics algorithm DYANA. J Mol Biol 319:209–227

    Article  CAS  PubMed  Google Scholar 

  • Hiller S, Fiorito F, Wüthrich K (2005) Automated projection spectroscopy (APSY). Proc Natl Acad Sci USA 102:10876–108881

    Article  CAS  PubMed  Google Scholar 

  • Hoch JC, Stern AS (2002) Maximum entropy reconstruction, spectrum analysis and deconvolution in multidimensional nuclear magnetic resonance. Methods Enzymol 338:159–178

    Article  Google Scholar 

  • Jakubowski JA, Kelley WP, Sweedler JV (2006) Screening for post-translational modifications in conotoxins using liquid chromatography/mass spectrometry: an important component of conotoxin discovery. Toxicon 47:688–699

    Article  CAS  PubMed  Google Scholar 

  • Jensen JE, Durek T, Alewood PF, Adams DJ, King GF, Rash LD (2009) Chemical synthesis and folding of APETx2, a potent and selective inhibitor of acid sensing ion channel 3. Toxicon 54:56–61

    Article  CAS  PubMed  Google Scholar 

  • Ji W, Zhang X, Hu H, Chen J, Gao Y, Liang S, An C (2005) Expression and purification of Huwentoxin-I in baculovirus system. Protein Expr Purif 41:454–458

    Article  CAS  PubMed  Google Scholar 

  • Jiang L, Peng L, Chen J, Zhang Y, Xiong X, Liang S (2008) Molecular diversification based on analysis of expressed sequence tags from the venom glands of the Chinese bird spider Ornithoctonus huwena. Toxicon 51:1479–1489

    Article  CAS  PubMed  Google Scholar 

  • Jiang L, Peng L, Zhang Y, Chen J, Zhang D, Liang S (2009) Expression, purification and characterization of a group of lectin-like peptides from the spider Ornithoctonus huwena. Peptides 30:669–674

    Article  CAS  PubMed  Google Scholar 

  • Kaas Q, Westermann JC, Halai R, Wang CK, Craik DJ (2008) ConoServer, a database for conopeptide sequences and structures. Bioinformatics (Oxford, England) 24:445–446

    Article  CAS  Google Scholar 

  • Kazimierczuk K, Koźmiński W, Zhukov I (2006) Two-dimensional Fourier transform of arbitrarily sampled NMR data sets. J Magn Reson 179:323–328

    Article  CAS  PubMed  Google Scholar 

  • King GF, Mobli M (2010) Determination of peptide and protein structures using NMR spectroscopy. In: Mander L, Liu H-W (eds) Comprehensive natural products chemistry II. Elsevier, Amsterdam

    Google Scholar 

  • Kita M, Black DS, Ohno O, Yamada K, Kigoshi H, Uemura D (2009) Duck-billed platypus venom peptides induce Ca2+ influx in neuroblastoma cells. J Am Chem Soc 131:18038–18039

    Article  CAS  PubMed  Google Scholar 

  • Kitaguchi T, Swartz KJ (2005) An inhibitor of TRPV1 channels isolated from funnel web spider venom. Biochemistry 44:15544–15549

    Article  CAS  PubMed  Google Scholar 

  • Kjeldsen F, Giessing AM, Ingrell CR, Jensen ON (2007) Peptide sequencing and characterization of post-translational modifications by enhanced ion-charging and liquid chromatography electron-transfer dissociation tandem mass spectrometry. Anal Chem 79:9243–9252

    Article  CAS  PubMed  Google Scholar 

  • Koehn FE, Carter GT (2005) The evolving role of natural products in drug discovery. Nat Rev Drug Discov 4:206–220

    Article  CAS  PubMed  Google Scholar 

  • Korolkova YV, Kozlov SA, Lipkin AV, Pluzhnikov KA, Hadley JK, Filippov AK, Brown DA, Angelo K, Strobaek D, Jespersen T, Olesen SP, Jensen BS, Grishin EV (2001) An ERG channel inhibitor from the scorpion Buthus eupeus. J Biol Chem 276:9868–9876

    Article  CAS  PubMed  Google Scholar 

  • Kozlov S, Malyavka A, McCutchen B, Lu A, Schepers E, Herrmann R, Grishin E (2005) A novel strategy for the identification of toxin like structures in spider venom. Proteins 59:131–140

    Article  CAS  PubMed  Google Scholar 

  • Krajewski JL, Dickerson IM, Potter LT (2001) Site-directed mutagenesis of m1-toxin 1: two amino acids responsible for stable toxin binding to M1 muscarinic receptors. Mol Pharmacol 60:725–731

    CAS  PubMed  Google Scholar 

  • Kupče Ē, Freeman R (2004) Projection-reconstruction technique for speeding up multidimensional NMR spectroscopy. J Am Chem Soc 126:6429–6440

    Article  PubMed  CAS  Google Scholar 

  • Legros C, Feyfant E, Sampieri F, Rochat H, Bougis PE, Martin-Eauclaire MF (1997) Influence of a NH2-terminal extension on the activity of KTX2, a K+ channel blocker purified from Androctonus australis scorpion venom. FEBS Lett 417:123–129

    Article  CAS  PubMed  Google Scholar 

  • Legros C, Kaabi H, El Ayeb M, Ceard B, Vacher H, Bougis PE, Martin-Eauclaire MF (2001) Use of fusion protein constructs to generate potent immunotherapy and protection against scorpion toxins. Vaccine 20:934–942

    Article  CAS  PubMed  Google Scholar 

  • Levandoski MM, Caffery PM, Rogowski RS, Lin Y, Shi Q-L, Hawrot E (2000) Recombinant expression of α-bungarotoxin in Pichia pastoris facilitates identification of mutant toxins engineered to recognize neuronal nicotinic acetylcholine receptors. J Neurochem 74:1279–1289

    Article  CAS  PubMed  Google Scholar 

  • Lewis RJ, Garcia ML (2003) Therapeutic potential of venom peptides. Nat Rev Drug Discov 2:790–802

    Article  CAS  PubMed  Google Scholar 

  • Liao Z, Cao J, Li S, Yan X, Hu W, He Q, Chen J, Tang J, Xie J, Liang S (2007) Proteomic and peptidomic analysis of the venom from Chinese tarantula Chilobrachys jingzhao. Proteomics 7:1892–1907

    Article  CAS  PubMed  Google Scholar 

  • Luan T, Orekhov VY, Gutmanas A, Billeter M (2005) Accuracy and robustness of three-way decomposition applied to NMR data. J Magn Reson 174:188–199

    Article  CAS  PubMed  Google Scholar 

  • Macarron R (2006) Critical review of the role of HTS in drug discovery. Drug Discov Today 11:277–279

    Article  PubMed  Google Scholar 

  • Macauley-Patrick S, Fazenda ML, McNeil B, Harvey LM (2005) Heterologous protein production using the Pichia pastoris expression system. Yeast 22:249–270

    Article  CAS  PubMed  Google Scholar 

  • Malmodin D, Billeter M (2005) Multiway decomposition of NMR spectra with coupled evolution periods. J Am Chem Soc 127:13486–13487

    Article  CAS  PubMed  Google Scholar 

  • Malone J, Trautmann M, Wilhelm K, Taylor K, Kendall DM (2009) Exenatide once weekly for the treatment of type 2 diabetes. Expert Opin Investig Drugs 18:359–367

    Article  CAS  PubMed  Google Scholar 

  • Miljanich GP (2004) Ziconotide: neuronal calcium channel blocker for treating severe chronic pain. Curr Med Chem 11:3029–3040

    CAS  PubMed  Google Scholar 

  • Mobli M, Maciejewski MW, Gryk MR, Hoch JC (2007a) An automated tool for maximum entropy reconstruction of biomolecular NMR spectra. Nat Methods 4:467–468

    Article  CAS  PubMed  Google Scholar 

  • Mobli M, Maciejewski MW, Gryk MR, Hoch JC (2007b) Automatic maximum entropy spectral reconstruction in NMR. J Biomol NMR 39:133–139

    Article  CAS  PubMed  Google Scholar 

  • Mobli M, Mijenović T, Bermel W, King GF (2009) ASAP-NMR: a high-throughput pipeline for rapid protein structure determination. In: Proceedings of third Asia-Pacific NMR symposium

  • Mobli M, Stern AS, Bermel W, King GF, Hoch JC (2010) A non-uniformly sampled 4D HCC(CO)NH-TOCSY experiment processed using maximum entropy for rapid protein sidechain assignment. J Magn Reson:in press

  • Newton KA, Clench MR, Deshmukh R, Jeyaseelan K, Strong PN (2007) Mass fingerprinting of toxic fractions from the venom of the Indian red scorpion, Mesobuthus tamulus: biotope-specific variation in the expression of venom peptides. Rapid Commun Mass Spectrom 21:3467–3476

    Article  CAS  PubMed  Google Scholar 

  • Noël F, Mendonça-Silva DL, Quintas LE (2001) Radioligand binding assays in the drug discovery process: potential pitfalls of high throughput screenings. Arzneimittel-Forschung 51:169–173

    PubMed  Google Scholar 

  • Olivera BM (2006) Conus peptides: biodiversity-based discovery and exogenomics. J Biol Chem 281:31173–31177

    Article  CAS  PubMed  Google Scholar 

  • Ortholand JY, Ganesan A (2004) Natural products and combinatorial chemistry: back to the future. Curr Opin Chem Biol 8:271–280

    Article  CAS  PubMed  Google Scholar 

  • Park SP, Kim BM, Koo JY, Cho H, Lee CH, Kim M, Na HS, Oh U (2008) A tarantula spider toxin, GsMTx4, reduces mechanical and neuropathic pain. Pain 137:208–217

    Article  CAS  PubMed  Google Scholar 

  • Paterson I, Anderson EA (2005) The renaissance of natural products as drug candidates. Science 310:451–453

    Article  PubMed  Google Scholar 

  • Peng K, Lin Y, Liang SP (2006) Nuclear magnetic resonance studies on huwentoxin-XI from the Chinese bird spider Ornithoctonus huwena: 15N labeling and sequence-specific 1H, 15N nuclear magnetic resonance assignments. Acta Biochim Biophys Sin (Shanghai) 38:457–466

    Article  CAS  Google Scholar 

  • Pham Trung N, Fitches E, Gatehouse JA (2006) A fusion protein containing a lepidopteran-specific toxin from the South Indian red scorpion (Mesobuthus tamulus) and snowdrop lectin shows oral toxicity to target insects. BMC Biotechnol 6:18

    Article  PubMed  CAS  Google Scholar 

  • Pimenta AM, Stocklin R, Favreau P, Bougis PE, Martin-Eauclaire MF (2001) Moving pieces in a proteomic puzzle: mass fingerprinting of toxic fractions from the venom of Tityus serrulatus (Scorpiones, Buthidae). Rapid Commun Mass Spectrom 15:1562–1572

    Article  CAS  PubMed  Google Scholar 

  • Prinz WA, Åslund F, Holmgren A, Beckwith J (1997) The role of the thioredoxin and glutaredoxin pathways in reducing protein disulfide bonds in the Escherichia coli cytoplasm. J Biol Chem 272:15661–15667

    Article  CAS  PubMed  Google Scholar 

  • Quinton L, Demeure K, Dobson R, Gilles N, Gabelica V, De Pauw E (2007) New method for characterizing highly disulfide-bridged peptides in complex mixtures: application to toxin identification from crude venoms. J Proteome Res 6:3216–3223

    Article  CAS  PubMed  Google Scholar 

  • Richardson M, Pimenta AM, Bemquerer MP, Santoro MM, Beirao PS, Lima ME, Figueiredo SG, Bloch C Jr, Vasconcelos EA, Campos FA, Gomes PC, Cordeiro MN (2006) Comparison of the partial proteomes of the venoms of Brazilian spiders of the genus Phoneutria. Comp Biochem Physiol C Toxicol Pharmacol 142:173–187

    Article  CAS  PubMed  Google Scholar 

  • Rivers DB, Crawley T, Bauser H (2005) Localization of intracellular calcium release in cells injured by venom from the ectoparasitoid Nasonia vitripennis (Walker) (Hymenoptera: Pteromalidae) and dependence of calcium mobilization on G-protein activation. J Insect Physiol 51:149–160

    Article  CAS  PubMed  Google Scholar 

  • Schroeder CI, Smythe ML, Lewis RJ (2004) Development of small molecules that mimic the binding of ω-conotoxins at the N-type voltage-gated calcium channel. Mol Divers 8:127–134

    Article  CAS  PubMed  Google Scholar 

  • Schwartz EF, Diego-Garcia E, Rodríguez de la Vega RC, Possani LD (2007) Transcriptome analysis of the venom gland of the Mexican scorpion Hadrurus gertschi (Arachnida: Scorpiones). BMC Genomics 8:119

    Article  PubMed  CAS  Google Scholar 

  • Seidler J, Zinn N, Boehm ME, Lehmann WD (2009) De novo sequencing of peptides by tandem mass spectrometry. Proteomics 10:634–649

    Article  CAS  Google Scholar 

  • Shao F, Xiong Y-M, Zhu R-H, Ling M-H, Chi C-W, Wang D-C (1999) Expression and purification of the BmK M1 neurotoxin from the scorpion Buthus martensii Karsch. Protein Expr Purif 17:358–365

    Article  CAS  PubMed  Google Scholar 

  • Shiu J-H, Chen C-Y, Chang L-S, Chen Y-C, Chen Y-C, Lo Y-H, Liu YC, Chuang W-J (2004) Solution structure of γ-bungarotoxin: the functional significance of amino acid residues flanking the RGD motif in integrin binding. Proteins 57:839–849

    Article  CAS  PubMed  Google Scholar 

  • Siemens J, Zhou S, Piskorowski R, Nikai T, Lumpkin EA, Basbaum AI, King D, Julius D (2006) Spider toxins activate the capsaicin receptor to produce inflammatory pain. Nature 444:208–212

    Article  CAS  PubMed  Google Scholar 

  • Sollod BL, Wilson D, Zhaxybayeva O, Gogarten JP, Drinkwater R, King GF (2005) Were arachnids the first to use combinatorial peptide libraries? Peptides 26:131–139

    Article  CAS  PubMed  Google Scholar 

  • Szyperski T, Wider G, Bushweller JH, Wüthrich K (1993) Reduced dimensionality in triple resonance NMR experiments. J Am Chem Soc 115:9307–9308

    Article  CAS  Google Scholar 

  • Taouji S, Dahan S, Bossé R, Chevet E (2009) Current screens based on the AlphaScreen technology for deciphering cell signalling pathways. Curr Genomics 10:93–101

    Article  CAS  PubMed  Google Scholar 

  • Tedford HW, Fletcher JI, King GF (2001) Functional significance of the β-hairpin in the insecticidal neurotoxin ω-atracotoxin-Hv1a. J Biol Chem 276:26568–26576

    Article  CAS  PubMed  Google Scholar 

  • Tedford HW, Sollod BL, Maggio F, King GF (2004) Australian funnel-web spiders: master insecticide chemists. Toxicon 43:601–618

    Article  CAS  PubMed  Google Scholar 

  • Ueberheide BM, Fenyo D, Alewood PF, Chait BT (2009) Rapid sensitive analysis of cysteine rich peptide venom components. Proc Natl Acad Sci USA 106:6910–6915

    Article  CAS  PubMed  Google Scholar 

  • Ullman EF, Kirakossian H, Singh S, Wu ZP, Irvin BR, Pease JS, Switchenko AC, Irvine JD, Dafforn A, Skold CN, Wagner DB (1994) Luminescent oxygen channeling immunoassay: measurement of particle binding kinetics by chemiluminescence. Proc Natl Acad Sci USA 91:5426–5430

    Article  CAS  PubMed  Google Scholar 

  • Ullman EF, Kirakossian H, Switchenko AC, Ishkanian J, Ericson M, Wartchow CA, Pirio M, Pease J, Irvin BR, Singh S, Singh R, Patel R, Dafforn A, Davalian D, Skold C, Kurn N, Wagner DB (1996) Luminescent oxygen channeling assay (LOCI): sensitive, broadly applicable homogeneous immunoassay method. Clin Chem 42:1518–1526

    CAS  PubMed  Google Scholar 

  • Vetter I, Lewis RJ (2009) Characterization of endogenous calcium responses in neuronal cell lines. Biochem Pharmacol 79:908–920

    Article  PubMed  CAS  Google Scholar 

  • Wang K, Yin S-J, Lu M, Yi H, Dai C, Xu X-J, Cao Z-J, Wu Y-L, Li W-X (2006) Functional analysis of the α-neurotoxin, BmαTX14, derived from the Chinese scorpion, Buthus martensii Karsch. Biotechnol Lett 28:1767–1772

    Article  CAS  PubMed  Google Scholar 

  • Wood DL, Miljenovic T, Cai S, Raven RJ, Kaas Q, Escoubas P, Herzig V, Wilson D, King GF (2009) ArachnoServer: a database of protein toxins from spiders. BMC Genomics 10:375

    Article  PubMed  CAS  Google Scholar 

  • Wu J-J, He L-L, Zhou Z, Chi C-W (2002) Gene expression, mutation, and structure-function relationship of scorpion toxin BmP05 active on SKCa channels. Biochemistry 41:2844–2849

    Article  CAS  PubMed  Google Scholar 

  • Wüthrich K (1986) NMR of proteins and nucleic acids. Wiley, New York

    Google Scholar 

  • Xu J, Wang X, Ensign B, Li M, Wu L, Guia A (2001) Ion-channel assay technologies: quo vadis? Drug Discov Today 6:1278–1287

    Article  CAS  PubMed  Google Scholar 

  • You WK, Jang YJ, Chung KH, Kim DS (2003) A novel disintegrin-like domain of a high molecular weight metalloprotease inhibits platelet aggregation. Biochem Biophys Res Commun 309:637–642

    Article  CAS  PubMed  Google Scholar 

  • Yuan C, Jin Q, Tang X, Hu W, Cao R, Yang S, Xiong J, Xie C, Xie J, Liang S (2007) Proteomic and peptidomic characterization of the venom from the Chinese bird spider, Ornithoctonus huwena Wang. J Proteome Res 6:2792–27801

    Article  CAS  PubMed  Google Scholar 

  • Zhang JH, Chung TD, Oldenburg KR (1999) A simple statistical parameter for use in evaluation and validation of high throughput screening assays. J Biomol Screen 4:67–73

    Article  PubMed  Google Scholar 

  • Zheng W, Spencer RH, Kiss L (2004) High throughput assay technologies for ion channel drug discovery. Assay Drug Dev Technol 2:543–552

    Article  CAS  PubMed  Google Scholar 

  • Zilberberg N, Gordon D, Pelhate M, Adams ME, Norris TM, Zlotkin E, Gurevitz M (1996) Functional expression and genetic alteration of an alpha scorpion neurotoxin. Biochemistry 35:10215–10222

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We acknowledge financial support from the Australian Research Council (Discovery Grants DP0774245 to GFK and DP0878450 to GFK and PFA) and the Australian National Health & Medical Research Council (Project Grant 511067 to LDR, GFK, and PFA, Program Grant 569927 to RJL and PFA, Senior Research Fellowship to RJL, and Australian Biomedical Training Fellowship to IV).

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  1. Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD, 4072, Australia

    Irina Vetter, Jasmine L. Davis, Lachlan D. Rash, Raveendra Anangi, Mehdi Mobli, Paul F. Alewood, Richard J. Lewis & Glenn F. King

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  1. Irina Vetter
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  2. Jasmine L. Davis
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  3. Lachlan D. Rash
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  4. Raveendra Anangi
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  8. Glenn F. King
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Correspondence to Glenn F. King.

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Vetter, I., Davis, J.L., Rash, L.D. et al. Venomics: a new paradigm for natural products-based drug discovery. Amino Acids 40, 15–28 (2011). https://doi.org/10.1007/s00726-010-0516-4

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  • DOI: https://doi.org/10.1007/s00726-010-0516-4

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