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Analytics for Bioactivity Profiling of Complex Mixtures with a Focus on Venoms

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Book cover Snake and Spider Toxins

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2068))

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Abstract

This chapter introduces bioactivity and bioaffinity terms in relation to mixture profiling and gives the significance of bioactivity and/or bioaffinity profiling of biologically active mixtures in general, and for bioactive mixtures in drug discovery research in particular. Further, the chapter gives an overview of the common and less common analytical approaches for bioactivity profiling of bioactive mixtures. Special focus is put on bioassay-guided fractionation as the standard technique employed (in identification and purification of bioactive molecules from a bioactive mixture), and on state-of-the-art post-column bioactivity profiling approaches, also providing examples and limitations of these analytical methods. On-column and pre-column bioactivity profiling analytics is also discussed. Examples of bioactive molecules identified and purified from different natural products are given with emphasis on molecules isolated from animal venoms. Finally, this chapter briefly discusses the importance of bioactivity profiling of metabolic mixtures in drug discovery.

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References

  1. Liu B, Li S, Hu J (2004) Technological advances in high-throughput screening. Am J Pharmacogenomics 4(4):263–276

    Article  CAS  PubMed  Google Scholar 

  2. Weller MG (2012) A unifying review of bioassay-guided fractionation, effect-directed analysis and related techniques. Sensors (Basel) 12(7):9181–9209

    Article  CAS  Google Scholar 

  3. Jonker W et al (2015) Methodologies for effect-directed analysis: environmental applications, food analysis, and drug discovery, in analyzing biomolecular interactions by mass spectrometry. Wiley-VCH, Weinheim, pp 109–163

    Google Scholar 

  4. Chen W et al (2015) Fasxiator, a novel factor XIa inhibitor from snake venom, and its site-specific mutagenesis to improve potency and selectivity. J Thromb Haemost 13(2):248–261

    Article  CAS  PubMed  Google Scholar 

  5. Graudins A et al (2012) Cloning and activity of a novel alpha-latrotoxin from red-back spider venom. Biochem Pharmacol 83(1):170–183

    Article  CAS  PubMed  Google Scholar 

  6. Feng J, Yang XW, Wang RF (2011) Bio-assay guided isolation and identification of alpha-glucosidase inhibitors from the leaves of Aquilaria sinensis. Phytochemistry 72(2–3):242–247

    Article  CAS  PubMed  Google Scholar 

  7. Crawford AD et al (2011) Zebrafish bioassay-guided natural product discovery: isolation of angiogenesis inhibitors from East African medicinal plants. PLoS One 6(2):e14694

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Eng Kiat Loo A, Huang D (2007) Assay-guided fractionation study of α-amylase inhibitors from Garcinia mangostana pericarp. J Agri Food Chem 55(24):9805–9810

    Article  CAS  Google Scholar 

  9. Su B-N et al (2002) Activity-guided fractionation of the seeds of Ziziphus jujuba using a cyclooxygenase-2 inhibitory assay. Planta Medica 68(12):1125–1128

    Article  CAS  PubMed  Google Scholar 

  10. Scher JM et al (2004) Bioactivity guided isolation of antifungal compounds from the liverwort Bazzania trilobata (L.) SF Gray. Phytochemistry 65(18):2583–2588

    Article  CAS  PubMed  Google Scholar 

  11. Ho CC, Kumaran A, Hwang LS (2009) Bio-assay guided isolation and identification of anti-Alzheimer active compounds from the root of Angelica sinensis. Food Chem 114(1):246–252

    Article  CAS  Google Scholar 

  12. Awad R et al (2009) Bioassay-guided fractionation of lemon balm (Melissa officinalis L.) using an in vitro measure of GABA transaminase activity. Phytotherapy Res 23(8):1075–1081

    Article  CAS  Google Scholar 

  13. Wu H et al (2013) Recent developments in qualitative and quantitative analysis of phytochemical constituents and their metabolites using liquid chromatography-mass spectrometry. J Pharm Biomed Anal 72:267–291

    Article  CAS  PubMed  Google Scholar 

  14. Bakker RA et al (2004) Constitutively active Gq/11-coupled receptors enable signaling by co-expressed G(i/o)-coupled receptors. J Biol Chem 279(7):5152–5161

    Article  CAS  PubMed  Google Scholar 

  15. Ohi N et al (1986) Semisynthetic Beta-Lactam antibiotics. 1. Synthesis and antibacterial activity of new ureidopenicillin derivatives having catechol moieties. J Antibiotics 39(2):230–241

    Article  CAS  Google Scholar 

  16. Elander RP (2003) Industrial production of beta-lactam antibiotics. Appl Microbiol Biotechnol 61(5–6):385–392

    Article  CAS  PubMed  Google Scholar 

  17. Kondo S, Hotta K (1999) Semisynthetic aminoglycoside antibiotics: development and enzymatic modifications. J Infect Chemother 5(1):1–9

    Article  CAS  PubMed  Google Scholar 

  18. Manzoni M, Rollini N (2002) Biosynthesis and biotechnological production of statins by filamentous fungi and application of these cholesterol-lowering drugs. Appl Microbiol Biotechnol 58(5):555–564

    Article  CAS  PubMed  Google Scholar 

  19. Jonker N et al (2011) Recent developments in protein-ligand affinity mass spectrometry. Anal Bioanal Chem 399(8):2669–2681

    Article  CAS  PubMed  Google Scholar 

  20. Kool J et al (2011) Advances in mass spectrometry-based post-column bioaffinity profiling of mixtures. Anal Bioanal Chem 399(8):2655–2668

    Article  CAS  PubMed  Google Scholar 

  21. Kinawi A, Teller C (1979) Determination of drug-albumin binding in buffered bovine serum-albumin solutions applying a modified ultrafiltration process. Arzneimittel-Forschung/Drug Res 29–2(10):1495–1500

    Google Scholar 

  22. Zlotos G et al (1998) Determination of protein binding of gyrase inhibitors by means of continuous ultrafiltration. Pergamon-Elsevier Science, Amsterdam

    Book  Google Scholar 

  23. Comess KM et al (2006) An ultraefficient affinity-based high-throughout screening process: application to bacterial cell wall biosynthesis enzyme MurF. J Biomol Screen 11(7):743–754

    Article  CAS  PubMed  Google Scholar 

  24. Li HL et al (2009) Screening and structural characterization of alpha-Glucosidase inhibitors from hawthorn leaf flavonoids extract by ultrafiltration LC-DAD-MSn and SORI-CID FTICR MS. J Am Soc Mass Spectrom 20(8):1496–1503

    Article  CAS  PubMed  Google Scholar 

  25. Ionita IA, Akhlaghi F (2010) Quantification of unbound prednisolone, prednisone, cortisol and cortisone in human plasma by ultrafiltration and direct injection into liquid chromatography tandem mass spectrometry. Ann Clin Biochem 47(Pt 4):350–357

    Article  CAS  PubMed  Google Scholar 

  26. Mulabagal V, Calderon AI (2010) Development of an ultrafiltration-liquid chromatography/mass spectrometry (UF-LC/MS) based ligand-binding assay and an LC/MS based functional assay for Mycobacterium tuberculosis shikimate kinase. Anal Chem 82(9):3616–3621

    Article  CAS  PubMed  Google Scholar 

  27. vanBreemen RB et al (1997) Pulsed ultrafiltration mass spectrometry: a new method for screening combinatorial libraries. Anal Chem 69(11):2159–2164

    Article  CAS  Google Scholar 

  28. Geun Shin Y, Bolton JL, van Breemen RB (2002) Screening drugs for metabolic stability using pulsed ultrafiltration mass spectrometry. Comb Chem High Throughput Screen 5(1):59–64

    Article  PubMed  Google Scholar 

  29. Liu DT et al (2007) Screening for ligands of human retinoid X receptor-alpha. Using ultrafiltration mass spectrometry. Anal Chem 79(24):9398–9402

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Cao H et al (2010) Discovery of cyclooxygenase inhibitors from medicinal plants used to treat inflammation. Pharmacol Res 61(6):519–524

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Annis DA et al (2004) A general technique to rank protein-ligand binding affinities and determine allosteric versus direct binding site competition in compound mixtures. J Am Chem Soc 126(47):15495–15503

    Article  CAS  PubMed  Google Scholar 

  32. Derks RJE et al (2006) SEC-MS as an approach to isolate and directly identifying small molecular GPCR-ligands from complex mixtures without labeling. Chromatographia 64(7–8):379–385

    Article  CAS  Google Scholar 

  33. Annis DA et al (2004) An affinity selection-mass spectrometry method for the identification of small molecule ligands from self-encoded combinatorial libraries—discovery of a novel antagonist of E-coli dihydrofolate reductase. Int J Mass Spectrom 238(2):77–83

    CAS  Google Scholar 

  34. Annis DA et al (2009) Inhibitors of the lipid phosphatase SHIP2 discovered by high-throughput affinity selection-mass spectrometry screening of combinatorial libraries. Comb Chem High Throughput Screen 12(8):760–771

    Article  CAS  PubMed  Google Scholar 

  35. Whitehurst CE et al (2006) Discovery and characterization of orthosteric and allosteric muscarinic M-2 acetylcholine receptor ligands by affinity selection-mass spectrometry. J Biomol Screen 11(2):194–207

    Article  CAS  PubMed  Google Scholar 

  36. Whitehurst CE, Annis DA (2008) Affinity selection-mass spectrometry and its emerging application to the high throughput screening of G protein-coupled receptors. Comb Chem High Throughput Screen 11(6):427–438

    Article  CAS  PubMed  Google Scholar 

  37. Jonker N et al (2008) Screening of protein-ligand interactions using dynamic protein-affinity chromatography solid-phase extraction-liquid chromatography-mass spectrometry. J Chromatogr A 1205(1–2):71–77

    Article  CAS  PubMed  Google Scholar 

  38. Hu F, Deng C, Zhang X (2008) Development of high performance liquid chromatography with immobilized enzyme onto magnetic nanospheres for screening enzyme inhibitor. J Chromatogr B 871(1):67–71

    Article  CAS  Google Scholar 

  39. Marsza MP et al (2008) Ligand and protein fishing with heat shock protein 90 coated magnetic beads. Anal Chem 80(19):7571–7575

    Article  CAS  Google Scholar 

  40. Jonker N et al (2009) Online magnetic bead dynamic protein-affinity selection coupled to LC-MS for the screening of pharmacologically active compounds. Anal Chem 81(11):4263–4270

    Article  CAS  PubMed  Google Scholar 

  41. Pochet L et al (2011) Online magnetic bead based dynamic protein affinity selection coupled to LC-MS for the screening of acetylcholine binding protein ligands. J Chromatogr B Analyt Technol Biomed Life Sci 879(20):1781–1788

    Article  CAS  PubMed  Google Scholar 

  42. Höfner G, Wanner KT (2015) MS binding assays. In: Analyzing biomolecular interactions by mass spectrometry. Wiley-VCH, Weinheim, pp 165–198

    Google Scholar 

  43. Zepperitz C, Hofner G, Wanner KT (2006) MS-binding assays: kinetic, saturation, and competitive experiments based on quantitation of bound marker as exemplified by the GABA transporter mGAT1. ChemMedChem 1(2):208–217

    Article  CAS  PubMed  Google Scholar 

  44. Singh NS, Jiang Z, Moaddel R (2015) Frontal and zonal affinity chromatography coupled to mass spectrometry. In: Analyzing biomolecular interactions by mass spectrometry. Wiley-VCH, Weinheim, pp 241–270

    Google Scholar 

  45. Loun B, Hage DS (1992) Characterization of thyroxine-albumin binding using high-performance affinity chromatography. I. Interactions at the warfarin and indole sites of albumin. J Chromatogr 579(2):225–235

    Article  CAS  PubMed  Google Scholar 

  46. Chan NW et al (2003) Frontal affinity chromatography-mass spectrometry assay technology for multiple stages of drug discovery: applications of a chromatographic biosensor. Anal Biochem 319(1):1–12

    Article  CAS  PubMed  Google Scholar 

  47. Moaddel R et al (2005) Enantioselective binding to the human organic cation transporter-1 (hOCT1) determined using an immobilized hOCT1 liquid chromatographic stationary phase. Chirality 17(8):501–506

    Article  CAS  PubMed  Google Scholar 

  48. Calleri E et al (2010) Frontal affinity chromatography-mass spectrometry useful for characterization of new ligands for GPR17 receptor. J Med Chem 53(9):3489–3501

    Article  CAS  PubMed  Google Scholar 

  49. Pharmaceuticals N. Tegretol (carbamazepine) extended-release tablets prescribing information. In N. Pharmaceuticals (ed). 2003

    Google Scholar 

  50. Haselberg R et al (2014) Capillary electrophoresis-based assessment of nanobody affinity and purity. Anal Chim Acta 818:1–6

    Article  CAS  PubMed  Google Scholar 

  51. Medina-Casanellas S et al (2012) Preparation and evaluation of an immunoaffinity sorbent for the analysis of opioid peptides by on-line immunoaffinity solid-phase extraction capillary electrophoresis-mass spectrometry. Anal Chim Acta 717:134–142

    Article  CAS  PubMed  Google Scholar 

  52. Haselberg R, Somsen GW (2015) Online affinity assessment and immunoaffinity sample pretreatment in capillary electrophoresis–mass spectrometry, in analyzing biomolecular interactions by mass spectrometry. Wiley-VCH, Weinheim, pp 271–298

    Google Scholar 

  53. Nijmeijer S et al (2012) Development of a profiling strategy for metabolic mixtures by combining chromatography and mass spectrometry with cell-based GPCR signaling. J Biomol Screen 17(10):1329–1338

    Article  CAS  PubMed  Google Scholar 

  54. Giera M et al (2009) Microfractionation revisited: a 1536 well high resolution screening assay. Anal Chem 81(13):5460–5466

    Article  CAS  PubMed  Google Scholar 

  55. Falck D et al (2013) Development of on-line liquid chromatography-biochemical detection for soluble epoxide hydrolase inhibitors in mixtures. Chromatographia 76(1–2):13–21

    Article  CAS  PubMed  Google Scholar 

  56. Oosterkamp AJ et al (1997) Theoretical concepts of on-line liquid chromatographic- biochemical detection systems II. Detection systems based on labelled affinity proteins. J Chromatogr A 787(1–2):37–46

    Article  CAS  Google Scholar 

  57. Oosterkamp AJ et al (1997) Theoretical concepts of on-line liquid chromatographic-biochemical detection systems. I. Detection systems based on labelled ligands. J Chromatogr A 787(1–2):27–35

    Article  CAS  PubMed  Google Scholar 

  58. Marques LA et al (2010) Production and on-line acetylcholinesterase bioactivity profiling of chemical and biological degradation products of tacrine. J Pharm Biomed Anal 53(3):609–616

    Article  CAS  PubMed  Google Scholar 

  59. Kool J et al (2007) Cytochrome P450 bio-affinity detection coupled to gradient HPLC: on-line screening of affinities to cytochrome P4501A2 and 2D6. J Chromatogr B 858(1):49–58

    Article  CAS  Google Scholar 

  60. Falck D et al (2010) Development of an online p38alpha mitogen-activated protein kinase binding assay and integration of LC-HR-MS. Anal Bioanal Chem 398(4):1771–1780

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Kool J et al (2010) Online fluorescence enhancement assay for the acetylcholine binding protein with parallel mass spectrometric identification. J Med Chem 53(12):4720–4730

    Article  CAS  PubMed  Google Scholar 

  62. de Vlieger JS et al (2010) Determination and identification of estrogenic compounds generated with biosynthetic enzymes using hyphenated screening assays, high resolution mass spectrometry and off-line NMR. J Chromatogr B Analyt Technol Biomed Life Sci 878(7–8):667–674

    Article  CAS  PubMed  Google Scholar 

  63. Schenk T et al (2003) A generic assay for phosphate-consuming or-releasing enzymes coupled on-line to liquid chromatography for lead finding in natural products. Anal Biochem 316(1):118–126

    Article  CAS  PubMed  Google Scholar 

  64. Hogenboom A et al (2001) Continuous-flow, on-line monitoring of biospecific interactions using electrospray mass spectrometry. Anal Chem 73(16):3816–3823

    Article  CAS  PubMed  Google Scholar 

  65. Heus F et al (2010) Development of a microfluidic confocal fluorescence detection system for the hyphenation of nano-LC to on-line biochemical assays. Anal Bioanal Chem 398(7–8):3023–3032

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Otvos RA et al (2013) Analytical workflow for rapid screening and purification of bioactives from venom proteomes. Toxicon 76:270–281

    Article  CAS  PubMed  Google Scholar 

  67. Heus F et al (2014) Miniaturized bioaffinity assessment coupled to mass spectrometry for guided purification of bioactives from toad and cone snail. Biology 3(1):139–156

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Heus F et al (2013) An efficient analytical platform for on-line microfluidic profiling of neuroactive snake venoms towards nicotinic receptor affinity. Toxicon 61:112–124

    Article  CAS  PubMed  Google Scholar 

  69. Giera M et al (2010) Structural elucidation of biologically active neomycin N-octyl derivatives in a regioisomeric mixture by means of liquid chromatography/ion trap time-of-flight mass spectrometry. Rapid Commun Mass Spectrom 24(10):1439–1446

    Article  CAS  PubMed  Google Scholar 

  70. Kool J et al (2012) High-resolution metabolic profiling towards G protein-coupled receptors: rapid and comprehensive screening of histamine H(4) receptor ligands. J Chromatogr A 1259:213–220

    Article  CAS  PubMed  Google Scholar 

  71. Mladic M et al (2016) At-line nanofractionation with parallel mass spectrometry and bioactivity assessment for the rapid screening of thrombin and factor Xa inhibitors in snake venoms. Toxicon 110:79–89

    Article  CAS  PubMed  Google Scholar 

  72. Mladic M et al (2017) Rapid screening and identification of ACE inhibitors in snake venoms using at-line nanofractionation LC-MS. Anal Bioanal Chem 409(25):5987–5997

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Still KS et al (2017) Multipurpose HTS coagulation analysis: assay development and assessment of coagulopathic snake venoms. Toxins (Basel) 9(12):382

    Article  CAS  Google Scholar 

  74. Bordon KC et al (2012) Isolation, enzymatic characterization and antiedematogenic activity of the first reported rattlesnake hyaluronidase from Crotalus durissus terrificus venom. Biochimie 94(12):2740–2748

    Article  CAS  PubMed  Google Scholar 

  75. Wiezel GA et al (2015) Identification of hyaluronidase and phospholipase B in Lachesis muta rhombeata venom. Toxicon 107(Pt B):359–368

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Babaie M et al (2013) Isolation and partial purification of anticoagulant fractions from the venom of the Iranian snake Echis carinatus. Acta Biochim Pol 60(1):17–20

    CAS  PubMed  Google Scholar 

  77. Menaldo DL et al (2015) Purification procedure for the isolation of a P-I metalloprotease and an acidic phospholipase A2 from Bothrops atrox snake venom. J Venom Anim Toxins Incl Trop Dis 21:28

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Osipov AV et al (2017) New paradoxical three-finger toxin from the cobra Naja kaouthia venom: Isolation and characterization. Dokl Biochem Biophys 475(1):264–266

    Article  CAS  PubMed  Google Scholar 

  79. Teixeira TL et al (2016) Isolation, characterization and screening of the in vitro cytotoxic activity of a novel L-amino acid oxidase (LAAOcdt) from Crotalus durissus terrificus venom on human cancer cell lines. Toxicon 119:203–217

    Article  CAS  PubMed  Google Scholar 

  80. Rodriguez-Acosta A et al (2016) Biological and biochemical characterization of venom from the broad-banded copperhead (Agkistrodon contortrix laticinctus): isolation of two new dimeric disintegrins. Anim Biol Leiden Neth 66(2):173–187

    Article  PubMed  PubMed Central  Google Scholar 

  81. Fucase TM et al (2017) Isolation and biochemical characterization of bradykinin-potentiating peptides from Bitis gabonica rhinoceros. J Venom Anim Toxins Incl Trop Dis 23:33

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. King GF (2011) Venoms as a platform for human drugs: translating toxins into therapeutics. Expert Opin Biol Ther 11(11):1469–1484

    Article  CAS  PubMed  Google Scholar 

  83. Ferreira SH, Bartelt DC, Greene LJ (1970) Isolation of bradykinin-potentiating peptides from Bothrops jararaca venom. Biochemistry 9(13):2583–2593

    Article  CAS  PubMed  Google Scholar 

  84. Ondetti MA et al (1971) Angiotensin-converting enzyme inhibitors from the venom of Bothrops jararaca. Isolation, elucidation of structure, and synthesis. Biochemistry 10(22):4033–4039

    Article  CAS  PubMed  Google Scholar 

  85. Smith CG, Vane JR (2003) The discovery of captopril. FASEB J 17(8):788–789

    Article  CAS  PubMed  Google Scholar 

  86. Scarborough RM (1999) Development of eptifibatide. Am Heart J 138(6 Pt 1):1093–1104

    Article  CAS  PubMed  Google Scholar 

  87. Cook JJ et al (1999) Tirofiban (Aggrastat (R)). Cardiovasc Drug Rev 17(3):199–224

    Article  CAS  Google Scholar 

  88. Earl ST et al (2012) Drug development from Australian elapid snake venoms and the Venomics pipeline of candidates for haemostasis: Textilinin-1 (Q8008), Haempatch (Q8009) and CoVase (V0801). Toxicon 59(4):456–463

    Article  CAS  PubMed  Google Scholar 

  89. Koh CY, Kini RM (2012) From snake venom toxins to therapeutics–cardiovascular examples. Toxicon 59(4):497–506

    Article  CAS  PubMed  Google Scholar 

  90. Vink S et al (2012) Natriuretic peptide drug leads from snake venom. Toxicon 59(4):434–445

    Article  CAS  PubMed  Google Scholar 

  91. Diochot S et al (2012) Black mamba venom peptides target acid-sensing ion channels to abolish pain. Nature 490(7421):552–555

    Article  CAS  PubMed  Google Scholar 

  92. Pu XC, Wong PT, Gopalakrishnakone P (1995) A novel analgesic toxin (hannalgesin) from the venom of king cobra (Ophiophagus hannah). Toxicon 33(11):1425–1431

    Article  CAS  PubMed  Google Scholar 

  93. McCleary RJ, Kini RM (2013) Non-enzymatic proteins from snake venoms: a gold mine of pharmacological tools and drug leads. Toxicon 62:56–74

    Article  CAS  PubMed  Google Scholar 

  94. Kini RM, Doley R (2010) Structure, function and evolution of three-finger toxins: mini proteins with multiple targets. Toxicon 56(6):855–867

    Article  CAS  PubMed  Google Scholar 

  95. Lewis RJ et al (2012) Conus venom peptide pharmacology. Pharmacol Rev 64(2):259–298

    Article  CAS  PubMed  Google Scholar 

  96. Twede VD et al (2009) Neuroprotective and cardioprotective conopeptides: an emerging class of drug leads. Curr Opin Drug Discov Devel 12(2):231–239

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Essack M, Bajic VB, Archer JA (2012) Conotoxins that confer therapeutic possibilities. Mar Drugs 10(6):1244–1265

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Vetter I, Lewis RJ (2012) Therapeutic potential of cone snail venom peptides (conopeptides). Curr Top Med Chem 12(14):1546–1552

    Article  CAS  PubMed  Google Scholar 

  99. Miljanich GP (2004) Ziconotide: neuronal calcium channel blocker for treating severe chronic pain. Curr Med Chem 11(23):3029–3040

    Article  CAS  PubMed  Google Scholar 

  100. Stöcklin R. XEP-018: a new myorelaxant peptide lead compound from the venom of the cone snail Conus consors. Proceedings of 7th Annual Peptide Therapeutics Symposium, 2012. p. 32

    Google Scholar 

  101. Furman BL (2012) The development of Byetta (exenatide) from the venom of the Gila monster as an anti-diabetic agent. Toxicon 59(4):464–471

    Article  CAS  PubMed  Google Scholar 

  102. Turton M et al (1996) A role for glucagon-like peptide-1 in the central regulation of feeding. Nature 379(6560):69–72

    Article  CAS  PubMed  Google Scholar 

  103. Doyle ME, Egan JM (2000) Glucagon-like peptide-1. Recent Prog Horm Res 56:377–399

    Article  Google Scholar 

  104. Klint JK et al (2012) Spider-venom peptides that target voltage-gated sodium channels: pharmacological tools and potential therapeutic leads. Toxicon 60(4):478–491

    Article  CAS  PubMed  Google Scholar 

  105. Mortari MR, Cunha AOS (2013) New perspectives in drug discovery using neuroactive molecules from the venom of arthropods. IntechOpen, London

    Google Scholar 

  106. Yang S et al (2013) Discovery of a selective NaV1. 7 inhibitor from centipede venom with analgesic efficacy exceeding morphine in rodent pain models. Proc Natl Acad Sci 110(43):17534–17539

    Article  PubMed  Google Scholar 

  107. Lewis RJ, Garcia ML (2003) Therapeutic potential of venom peptides. Nat Rev Drug Discov 2(10):790–802

    Article  CAS  PubMed  Google Scholar 

  108. Mathias NR, Hussain MA (2010) Non-invasive systemic drug delivery: developability considerations for alternate routes of administration. J Pharm Sci 99(1):1–20

    Article  CAS  PubMed  Google Scholar 

  109. Anderson S (2005) Making medicines: a brief history of pharmacy and pharmaceuticals. Pharmaceutical Press, London

    Google Scholar 

  110. Hamilton GR, Baskett TF (2000) In the arms of Morpheus the development of morphine for postoperative pain relief. Can J Anaesth 47(4):367–374

    Article  CAS  PubMed  Google Scholar 

  111. Sneader W (1996) Drug prototypes and their exploitation. Wiley, Chichester

    Google Scholar 

  112. Newman DJ, Cragg GM (2012) Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat Prod 75(3):311–335

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Koehn FE, Carter GT (2005) The evolving role of natural products in drug discovery. Nat Rev Drug Discov 4(3):206–220

    Article  CAS  PubMed  Google Scholar 

  114. Harvey AL (2008) Natural products in drug discovery. Drug Discov Today 13(19–20):894–901

    Article  CAS  PubMed  Google Scholar 

  115. Harvey AL (2014) Toxins and drug discovery. Toxicon 92:193–200

    Article  CAS  PubMed  Google Scholar 

  116. Cragg GM, Newman DJ (2013) Natural products: a continuing source of novel drug leads. Biochim Biophys Acta 1830(6):3670–3695

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Chin YW et al (2006) Drug discovery from natural sources. AAPS J 8(2):E239–E253

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Fabricant DS, Farnsworth NR (2001) The value of plants used in traditional medicine for drug discovery. Environ Health Perspect 109(Suppl 1):69–75

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Hanks GW et al (2001) Morphine and alternative opioids in cancer pain: the EAPC recommendations. Br J Cancer 84(5):587–593

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Furlan AD et al (2006) Opioids for chronic noncancer pain: a meta-analysis of effectiveness and side effects. CMAJ 174(11):1589–1594

    Article  PubMed  PubMed Central  Google Scholar 

  121. Campbell TJ, Williams KM (2001) Therapeutic drug monitoring: antiarrhythmic drugs. Br J Clin Pharmacol 52:21s–34s

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Barnes PJ (2006) Theophylline for COPD. Thorax 61(9):742–744

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Barnes PJ (2001) Tiotropium bromide. Expert Opin Investig Drugs 10(4):733–740

    Article  CAS  PubMed  Google Scholar 

  124. Hansel TT, Barnes PJ (2002) Tiotropium bromide: a novel once-daily anticholinergic bronchodilator for the treatment of COPD. Drugs Today (Barc) 38(9):585–600

    Article  CAS  Google Scholar 

  125. Elliott WJ, Ram CV (2011) Calcium channel blockers. J Clin Hypertens (Greenwich) 13(9):687–689

    Article  CAS  Google Scholar 

  126. Bailey CJ, Day C (2004) Metformin: its botanical background. Pract Diab Int 21(3):115–117

    Article  Google Scholar 

  127. Ruetsch YA, Boni T, Borgeat A (2001) From cocaine to ropivacaine: the history of local anesthetic drugs. Curr Top Med Chem 1(3):175–182

    Article  CAS  PubMed  Google Scholar 

  128. Raghavendra T (2002) Neuromuscular blocking drugs: discovery and development. J R Soc Med 95(7):363–367

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Graziose R, Lila MA, Raskin I (2010) Merging traditional Chinese medicine with modern drug discovery technologies to find novel drugs and functional foods. Curr Drug Discov Technol 7(1):2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Gong X, Sucher NJ (1999) Stroke therapy in traditional Chinese medicine (TCM): prospects for drug discovery and development. Trends Pharmacol Sci 20(5):191–196

    Article  CAS  PubMed  Google Scholar 

  131. Hsiao W, Liu L (2010) The role of traditional Chinese herbal medicines in cancer therapy—from TCM theory to mechanistic insights. Planta Medica 76(11):1118

    Article  CAS  PubMed  Google Scholar 

  132. Lao L, Xu L, Xu S (2012) Traditional Chinese medicine. In: Integrative pediatric oncology. Springer, Beijing, pp 125–135

    Chapter  Google Scholar 

  133. Scriabine A (1999) Discovery and development of major drugs currently in use. In: Pharmaceutical innovation: revolutionizing human health. Chemical Heritage Press, Philadelphia, pp 148–270

    Google Scholar 

  134. Page MG (2012) Beta-lactam antibiotics. In: Antibiotic discovery and development. Springer, New York, pp 79–117

    Chapter  Google Scholar 

  135. Chopra I, Roberts M (2001) Tetracycline antibiotics: mode of action, applications, molecular biology, and epidemiology of bacterial resistance. Microbiol Mol Biol Rev 65(2):232–260; second page, table of contents

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Forge A, Schacht J (2000) Aminoglycoside antibiotics. Audiol Neurootol 5(1):3–22

    Article  CAS  PubMed  Google Scholar 

  137. Omura S (2002) Macrolide antibiotics: chemistry, biology, and practice. Academic Press, Orlando

    Google Scholar 

  138. Berdy J (2005) Bioactive microbial metabolites. J Antibiot (Tokyo) 58(1):1–26

    Article  CAS  Google Scholar 

  139. Colombo D, Ammirati E (2011) Cyclosporine in transplantation—a history of converging timelines. J Biol Regul Homeost Agents 25(4):493–504

    CAS  PubMed  Google Scholar 

  140. Craik DJ et al (2013) The future of peptide-based drugs. Chem Biol Drug Des 81(1):136–147

    Article  CAS  PubMed  Google Scholar 

  141. Kola I, Landis J (2004) Can the pharmaceutical industry reduce attrition rates? Nat Rev Drug Discov 3(8):711–716

    Article  CAS  PubMed  Google Scholar 

  142. Cusack KP et al (2013) Emerging technologies for metabolite generation and structural diversification. Bioorg Med Chem Lett 23(20):5471–5483

    Article  CAS  PubMed  Google Scholar 

  143. Dhont M (2010) History of oral contraception. Eur J Contracept Reprod Health Care 15(S2):S12–S18

    Article  PubMed  Google Scholar 

  144. Lin JH, Lu AY (1997) Role of pharmacokinetics and metabolism in drug discovery and development. Pharmacol Rev 49(4):403–449

    CAS  PubMed  Google Scholar 

  145. Mladic M et al (2015) At-line coupling of LC-MS to bioaffinity and selectivity assessment for metabolic profiling of ligands towards chemokine receptors CXCR1 and CXCR2. J Chromatogr B Analyt Technol Biomed Life Sci 1002:42–53

    Article  CAS  PubMed  Google Scholar 

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Mladic, M., Niessen, W.M.A., Somsen, G.W., Kool, J. (2020). Analytics for Bioactivity Profiling of Complex Mixtures with a Focus on Venoms. In: Priel, A. (eds) Snake and Spider Toxins. Methods in Molecular Biology, vol 2068. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9845-6_2

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  • DOI: https://doi.org/10.1007/978-1-4939-9845-6_2

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