Abstract
The analyst faces a couple of challenges when screening complex mixtures. Over the past decades, several strategies were developed to overcome these problems. The review presented here provides an overview of the different strategies on the integration of separation sciences, mass spectrometry, and bioactivity screening in a single platform to allow the simultaneous screening and characterization of complex mixtures. The applied strategies can generally be categorized into precolumn and postcolumn principles. While the precolumn methodologies mainly include affinity-based screening, the postcolumn strategies can also employ enzyme activity assays. The different subtypes of these philosophies will be discussed and examples for each of the techniques are presented.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Abbreviations
- Ach:
-
Acetylcholine
- AChE:
-
Acetylcholinesterase
- AD:
-
Alzheimer’s disease
- ALIS:
-
Automated ligand identification system
- AMQI:
-
7-acetoxy-1-methylquinolinium iodide
- BCD:
-
Biochemical detection
- EDA:
-
Effect-directed analysis
- EGFR:
-
Endothelial growth factor receptor
- ESI:
-
Electrospray ionization
- ESI-MS:
-
Electrospray ionization mass spectrometry
- FAC:
-
Frontal affinity chromatography
- hERα:
-
Human estrogen receptor α
- hERβ:
-
Human estrogen receptor β
- HMQI:
-
7-hydroxy-1-methylquinolinium iodide
- HPLC:
-
High performance liquid chromatography
- IAM:
-
Immobilized artifical membrane
- K d :
-
Dissociation constant
- LC:
-
Liquid chromatography
- LC-MS:
-
Liquid chromatography mass spectrometry
- MMP3:
-
Human matrix metalloprotease 3
- MS:
-
Mass spectrometry
- NET:
-
Norethisterone
- PAB:
-
Paramagnetic affinity beads
- PDA:
-
Photo diode array
- SDH:
-
Sorbitoldehydrogenase
- SEC:
-
Size exclusion chromatography
- SMT:
-
System monitoring trace
- SPE:
-
Solid phase extraction
- TIC:
-
Total ion chromatogram
References
Koehn FE (2008) New strategies and methods in the discovery of natural product anti-infective agents: the mannopeptimycins. J Med Chem 51:2613–2617
Barceló D (2007) Effect-directed analysis of key toxicants in european river basins. A review. Environ Sci Pollut Res 14:30–38
Lübcke-von Varel U, Streck G, Brack W (2008) Automated fractionation procedure for polycyclic aromatic compounds in sediment extracts on three coupled normal-phase high-performance liquid chromatography columns. J Chromatogr A 1185:31–42
Koehn FE, Carter GT (2005) The evolving role of natural products in drug discovery. Nat Rev Drug Discov 4:206–220
Newman DJ, Cragg GM (2007) Natural products as sources of new drugs over the last 25 years. J Nat Prod 70:461–477
Blundell TL, Jhoti H, Abell C (2002) High-throughput crystallography for lead discovery in drug design. Nat Rev Drug Discov 1:45–54
Harvey AL (2007) Natural products as a screening resource. Curr Opin Chem Biol 11:480–484
Brack W (2003) Effect-directed analysis: a promising tool for the identification of organic toxicants in complex mixtures? Anal Bioanal Chem 377:397–407
Tuulia H (2009) Novel sample extraction and chromatographic techniques for environmental analysis. LC-GC Europe 22:172–179
Brack W, Schmitt-Jansen M, Machala M et al (2008) How to confirm identified toxicants in effect-directed analysis. Anal Bioanal Chem 390:1959–1973
He H, Williamson RT, Shen B et al (2002) Mannopeptimycins, novel antibacterial glycopeptides from Streptomyces hygroscopicus, LL-AC98. J Am Chem Soc 124:9729–9736
Jonker N, Kool J, Krabbe JG et al (2008) Screening of protein-ligand interactions using dynamic protein-affinity chromatography solid-phase extraction-liquid chromatography-mass spectrometry. J Chromatogr A 1205:71–77
Jonker N, Kretschmer A, Kool J et al (2009) Online magnetic bead dynamic protein-affinity selection coupled to LC/MS for the screening of pharmacologically active compounds. Anal Chem 81:4263–4270
Muckenschnabel I, Falchetto R, Mayr LM et al (2004) SpeedScreen: label-free liquid chromatography-mass spectrometry-based high-throughput screening for the discovery of orphan protein ligands. Anal Biochem 324:241–249
Brack W, Kind T, Hollert H et al (2003) Sequential fractionation procedure for the identification of potentially cytochrome P4501A-inducing compounds. J Chromatogr A 986:55–66
Tammela P, Wennberg T, Vuorela H et al (2004) HPLC micro-fractionation coupled to a cell-based assay for automated on-line primary screening of calcium antagonistic components in plant extracts. Anal Bioanal Chem 380:614–618
de Boer AR, Lingeman H, Niessen WMA et al (2007) Mass spectrometry-based biochemical assays for enzyme-inhibitor screening. Trends Analyt Chem 26:867–883
de Jong CF, Derks RJE, Bruyneel B et al (2006) High-performance liquid chromatography-mass spectrometry-based acetylcholinesterase assay for the screening of inhibitors in natural extracts. J Chromatogr A 1112:303–310
Oosterkamp AJ, Irth H, Tjaden UR et al (1997) Theoretical concepts of on-line liquid chromatographic- biochemical detection systems II. Detection systems based on labelled affinity proteins. J Chromatogr A 787:37–46
Oosterkamp AJ, Irth H, Villaverde Herraiz MT et al (1997) Theoretical concepts of on-line liquid chromatographic-biochemical detection systems I. Detection systems based on labelled ligands. J Chromatogr A 787:27–35
Schebb N, Faber H, Maul R et al (2009) Analysis of glutathione adducts of patulin by means of liquid chromatography (HPLC) with biochemical detection (BCD) and electrospray ionization tandem mass spectrometry (ESI-MS/MS). Anal Bioanal Chem 394:1361–1373
Giera M, Heus F, Janssen L et al (2009) Microfractionation revisited: a 1536 well high resolution screening assay. Anal Chem 81:5460–5466
Annis DA, Nickbarg E, Yang X et al (2007) Affinity selection-mass spectrometry screening techniques for small molecule drug discovery. Curr Opin Chem Biol 11:518–526
Deng G, Sanyal G (2006) Applications of mass spectrometry in early stages of target based drug discovery. J Pharm Biomed Anal 40:528–538
Schriemer DC, Bundle DR, Li L et al (1998) Micro-scale frontal affinity chromatography with mass spectrometric detection: a new method for the screening of compound libraries. Angew Chem Int Ed Engl 37:3383–3387
Calleri E, Temporini C, Caccialanza G et al (2009) Target-based drug discovery: the emerging success of frontal affinity chromatography coupled to mass spectrometry. ChemMedChem 4:905–916
Moaddel R, Calleri E, Massolini G et al (2007) The synthesis and initial characterization of an immobilized purinergic receptor (P2Y1) liquid chromatography stationary phase for online screening. Anal Biochem 364:216–218
Ng W, Dai J-R, Slon-Usakiewicz JJ et al (2007) Automated multiple ligand screening by frontal affinity chromatography-mass spectrometry (FAC-MS). J Biomol Screen 12:167–174
Kasai K-I, Oda Y, Nishikata M et al (1986) Frontal affinity chromatography: theory for its application to studies on specific interactions of biomolecules. J Chromatogr B Biomed Sci Appl 376:33–47
Kelly MA, McLellan TJ, Rosner PJ (2001) Strategic use of affinity-based mass spectrometry techniques in the drug discovery process. Anal Chem 74:1–9
Luo H, Chen L, Li Z et al (2003) Frontal immunoaffinity chromatography with mass spectrometric detection: a method for finding active compounds from traditional Chinese herbs. Anal Chem 75:3994–3998
Zhu L, Chen L, Luo H et al (2003) Frontal affinity chromatography combined on-line with mass spectrometry: a tool for the binding study of different epidermal growth factor receptor inhibitors. Anal Chem 75:6388–6393
Moaddel R, Bullock PL, Wainer IW (2004) Development and characterization of an open tubular column containing immobilized P-glycoprotein for rapid on-line screening for P-glycoprotein substrates. J Chromatogr B 799:255–263
Cancilla MT, Leavell MD, Chow J et al (2000) Mass spectrometry and immobilized enzymes for the screening of inhibitor libraries. Proc Natl Acad Sci U S A 97:12008–12013
Ferrance JP (2007) Gellan beads as a transparent media for protein immobilization and affinity capture. J Chromatogr A 1165:86–92
Schlosser G, Vekéy K, Malorni A et al (2005) Combination of solid-phase affinity capture on magnetic beads and mass spectrometry to study non-covalent interactions: example of minor groove binding drugs. Rapid Commun Mass Spectrom 19:3307–3314
Hu F, Zhang H, Lin H et al (2008) Enzyme inhibitor screening by electrospray mass spectrometry with immobilized enzyme on magnetic silica microspheres. J Am Soc Mass Spectrom 19:865–873
Siemoneit U, Hofmann B, Kather N et al (2008) Identification and functional analysis of cyclooxygenase-1 as a molecular target of boswellic acids. Biochem Pharmacol 75:503–513
Cloutier TE, Comess KM (2007) In: Wanner K, Höfner G (ed) Mass spectrometry in medicinal chemistry, VCH, Weinheim, pp 157–184
van Breemen RB, Huang C-R, Nikolic D et al (1997) Pulsed ultrafiltration mass spectrometry: a new method for screening combinatorial libraries. Anal Chem 69:2159–2164
Wickramasinghe SR, Bower SE, Chen Z et al (2009) Relating the pore size distribution of ultrafiltration membranes to dextran rejection. J Memb Sci 340:1–8
Zhang H, Gu Q, Liang X et al (2004) Screening for topoisomerase I binding compounds by high-performance liquid chromatography-mass spectrometry. Anal Biochem 329:173–179
Comess KM, Schurdak ME, Voorbach MJ et al (2006) An ultraefficient affinity-based high-throughout screening process: application to bacterial cell wall biosynthesis enzyme MurF. J Biomol Screen 11:743–754
Wen J, Arakawa T, Philo JS (1996) Size-exclusion chromatography with on-line light-scattering, absorbance, and refractive index detectors for studying proteins and their interactions. Anal Biochem 240:155–166
Wabnitz PA, Loo JA (2002) Drug screening of pharmaceutical discovery compounds by micro-size exclusion chromatography/mass spectrometry. Rapid Commun Mass Spectrom 16:85–91
Blom KF, Larsen BS, McEwen CN (1998) Determining affinity-selected ligands and estimating binding affinities by online size exclusion chromatography/liquid chromatography-mass spectrometry. J Comb Chem 1:82–90
Dastmalchi K, Ollilainen V, Lackman P et al (2009) Acetylcholinesterase inhibitory guided fractionation of Melissa officinalis L. Bioorg Med Chem 17:867–871
Scher JM, Speakman J-B, Zapp J et al (2004) Bioactivity guided isolation of antifungal compounds from the liverwort Bazzania trilobata (L.) S.F. Gray. Phytochemistry 65:2583–2588
Giera M, Plössl F, Bracher F (2007) Fast and easy in vitro screening assay for cholesterol biosynthesis inhibitors in the post-squalene pathway. Steroids 72:633–642
Giera M, Renard D, Plössl F et al (2008) Lathosterol side chain amides-A new class of human lathosterol oxidase inhibitors. Steroids 73:299–308
Renard D, Perruchon J, Giera M et al (2009) Side chain azasteroids and thiasteroids as sterol methyltransferase inhibitors in ergosterol biosynthesis. Bioorg Med Chem 17:8123–8137
Bugni T, Harper M, McCulloch M et al (2008) Fractionated marine invertebrate extract libraries for drug discovery. Molecules 13:1372–1383
Wolfender JL, Queiroz EF, Hostettmann K (2005) Phytochemistry in the microgram domain: a LC-NMR perspective. Magn Res Chem 43:697–709
Berg M, Undisz K, Thiericke R et al (2001) Evaluation of liquid handling conditions in microplates. J Biomol Screen 6:47–56
de Boer AR, Alcaide-Hidalgo JM, Krabbe JG et al (2005) High-temperature liquid chromatography coupled on-line to a continuous-flow biochemical screening assay with electrospray ionization mass spectrometric detection. Anal Chem 77:7894–7900
Hirata J, Ariese F, Gooijer C et al (2003) Continuous-flow protease assay based on fluorescence resonance energy transfer. Anal Chim Acta 478:1–10
In Kyung R, Natalie A, Teus L et al (2003) Determining acetylcholinesterase inhibitory activity in plant extracts using a fluorimetric flow assay. Phytochem Anal 14:145–149
Shi S-Y, Zhang Y-P, Jiang X-Y et al (2009) Coupling HPLC to on-line, post-column (bio)chemical assays for high-resolution screening of bioactive compounds from complex mixtures. Trends Analyt Chem 28:865–877
Letzel T (2008) Real-time mass spectrometry in enzymology. Anal Bioanal Chem 390:257–261
Schenk T, Appels NMGM, van Elswijk DA 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 316:118–126
de Boer AR, Letzel T, van Elswijk DA et al (2004) On-line coupling of high-performance liquid chromatography to a continuous-flow enzyme assay based on electrospray ionization mass spectrometry. Anal Chem 76:3155–3161
Schebb NH, Heus F, Saenger T et al (2008) Development of a countergradient parking system for gradient liquid chromatography with online biochemical detection of serine protease inhibitors. Anal Chem 80:6764–6772
Sabbagh MN (2009) Drug development for Alzheimer’s disease: where are we now and where are we headed? Am J Geriatr Pharmacother 7:167–185
Ingkaninan K, Hazekamp A, de Best CM et al (2000) The application of HPLC with on-line coupled uv/ms-biochemical detection for isolation of an acetylcholinesterase inhibitor from Narcissus ‘Sir Winston Churchill’. J Nat Prod 63:803–806
de Vlieger JSB, Kolkman AJ, Ampt KAM 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 878:667–674
de Boer AR, Bruyneel B, Krabbe JG et al (2005) A microfluidic-based enzymatic assay for bioactivity screening combined with capillary liquid chromatography and mass spectrometry. Lab Chip 5:1286–1292
Suda TA H, Hamada M, Takeuchi T, Umezawa H (1972) Antipain, a new protease inhibitor isolated from Actinomycetes. J Antibiot 25:263–265
Barrett AJ, Kembhavi AA, Brown MA et al (1982) L-trans-Epoxysuccinyl-leucylamido(4-guanidino)butane (E-64) and its analogues as inhibitors of cysteine proteinases including cathepsins B, H and L. Biochem J 201:189–198
Giera M, de Vlieger JSB, Lingeman H 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 24:1439–1446
Hecker M, Hollert H (2009) Effect-directed analysis (EDA) in aquatic ecotoxicology: state of the art and future challenges. Environ Sci Pollut Res 16:607–613
Kuch B, Kern F, Metzger JW et al (2010) Effect-related monitoring: estrogen-like substances in groundwater. Environ Sci Pollut Res 17:250–260
Roepcke CBS, Muench SB, Schulze H et al (2010) Analysis of phosphorothionate pesticides using a chloroperoxidase pretreatment and acetylcholinesterase biosensor detection. J Agric Food Chem 58:8748–8756
Kool J, de Kloe GE, Bruyneel B et al (2010) Online fluorescence enhancement assay for the acetylcholine binding protein with parallel mass spectrometric identification. J Med Chem 53:4720–4730
Liu PS, Lin CM, Pan CY et al (2003) Butyl benzyl phthalate blocks Ca2+ signaling and catecholamine secretion coupled with nicotinic acetylcholine receptors in bovine adrenal chromaffin cells. Neurotoxicology 24:97–105
Kim SM, Park JG, Baek WK et al (2008) Cadmium specifically induces MKP-1 expression via the glutathione depletion-mediated p38 MAPK activation in C6 glioma cells. Neurosci Lett 440:289–293
Hermansson V, Asp V, Bergman Å et al (2007) Comparative CYP-dependent binding of the adrenocortical toxicants 3-methylsulfonyl–DDE and o, p′-DDD in Y-1 adrenal cells. Arch Toxicol 81:793–801
Kaisarevic S, von Varel UL, Orcic D et al (2009) Effect-directed analysis of contaminated sediment from the wastewater canal in Pancevo industrial area, Serbia. Chemosphere 77:907–913
Acknowledgments
The work of the author M. Giera was supported by the German Academic Exchange program (DAAD).
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2011 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Giera, M., Irth, H. (2011). Simultaneous Screening and Chemical Characterization of Bioactive Compounds Using LC-MS-Based Technologies (Affinity Chromatography). In: Brack, W. (eds) Effect-Directed Analysis of Complex Environmental Contamination. The Handbook of Environmental Chemistry(), vol 15. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-18384-3_6
Download citation
DOI: https://doi.org/10.1007/978-3-642-18384-3_6
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-18383-6
Online ISBN: 978-3-642-18384-3
eBook Packages: Earth and Environmental ScienceEarth and Environmental Science (R0)