Abstract
Protein microarrays are a relatively new technology, which will dramatically impact the pharmaceutical industry. The critical need for more rapid identification of novel drug targets, and for obtaining high-quality information early in the target validation process is a major driver for the industry. High-throughput protein analytical techniques are critical for obtaining biological information beyond that which transcript analysis can provide, given that proteins are the "worker bees" in cells. The vast complexity of proteins when compared to DNA and RNA in terms of sheer number, and structural and biochemical diversity requires a higher degree of sophistication in both assay design and data analysis. High-throughput microarray technology platforms allow for simultaneous, multi-parametric analysis of complex protein mixtures. Protein microarrays have tremendous potential as a tool for the study of protein–protein, enzyme–substrate, and antibody–antigen interactions among others. They can also be used for biomarkers and drug target identification via comparative proteomic analysis of healthy and disease tissues. More recently, cellular microarrays that enable identification of cell-surface receptors and other cell-surface proteins allowing rapid screening of cell-specific, novel drug targets, are being developed. This review will focus on the technical issues and potential applications of protein microarrays in pharmaceutical discovery.
Similar content being viewed by others
References
DeRisi JL, Iyer VR, Brown PO (1997) Science 278:680–686
Gerhold D, Rushmore T, Caskey CT (1999) Trends Biochem 24:168–173
Anderson L, Seilhamer J (1997) Electrophoresis 18:533–537
Griffin TJ, Gygi SP, Ideker T, Rist B, Eng J, Hood L, Aebersold R (2002) Mol Cell Proteomics 1:323–333
Ekins RP (1989) J Pharm Biomed Anal 7:155–168
Haab BB, Dunham MJ, Brown PO (2000) Genome Biol 2:4.1
MacBeath G, Schreiber SS (2000) Science 289:1760–1763
Cunningham MJ (2001) J Pharmacol Toxicol Methods 44:291–300
Schäferling M, Kruschina M, Meerkamp M, Ortigao F, Kambhampati D (2002) PharmaGenomics 1:37–44
Guschin D, Yershov G, Zaslavsky A, Gemmell A, Shick V, Proudnikov D, Arenkov P, Mirzabekov A (1997) Anal Biochem 250:203–211
Tam SW, Weise R, Lee S, Gilmore J, Kumble KD (2002) J Immunol Methods 261:157–165
Afanassiev V, Hanemann V, Wolfl S (2000) Nucleic Acids Res 28:e66
Arenkov PA, Kukhtin A, Gemmell S, Voloshchuk V, Chupeeva V, Mirzabekov A (2000) Anal Biochem 278:123–131
Stillman BA, Tonkinson JL (2000) Biotechniques 29:630–635
Stolowitz ML, Ahlem C, Hughes KA, Kaiser RJ, Kesicki EA, Li G, Lund KP, Torkelson SM, Wiley JP (2001) Bioconjug Chem 12:229–239
Zhu H, Klemic JF, Chang S, Bertone P, Casamayor A, Klemic KG, Smith D, Gerstein M, Reed MA, Snyder M (2000) Nature Genetics 26:283–289
Mooney JF, Hunt AJ, McIntosh JR, Liberko CA, Walba DM, Rogers CT (1996) Proc Natl Acad Sci USA 93:12287–12291
Moody MD, Van Arsdell SW, Murphy KP, Orencole SF, Burns C (2001) BioTechniques 31:186–194
Holt LJ, Enever C, de Wildt RM, Tomlinson IM (2000) Curr Opin Biotechnol 11:445–449
Sreekumar A, Nyati MK, Varambally S, Barrette TR, Ghosh D, Lawrence TS, Chinnaiyan, AM (2001) Cancer Res 61:7585–7593
Knezevic V, Leethanakul C, Bichsel VE, Worth JM, Prabhu VV, Silvio Gutkind J, Liotta LA, Munson PJ, Petricoin EF, Krizman DB (2001) Proteomics 1:1271–1278
Johnson PJ (2000) Ann New York Acad Sci 945:8-21
Zhu H, Bilgin M, Bangham R, Hall D, Casamayor A, Bertone P, Lan N, Jansen R, Bidlingmaier S, Houfek T, Mitchell T, Miller P, Dean RA, Gerstein M, Snyder M (2001) Science
Bieri C, Ernst OP, Heyse S, Hofmann KP, Vogel H (2001) Nature Biotech 17:1005–1108
Fang Y, Frutos AG, Lahiri J (2002) ChemBioChem 3:987–991
Stephan JP, Schanz S, Wong A, Schow P, Wong WLT (2002) Am J Path 161:787–797
Houseman BT, Huh JH, Kron SJ, Mrksich M (2002) Nature Biotechnol 20:270–274
Falsey JR, Renil M, Park S, Li S, Lam KS (2001) Bioconjugate Chem 12:346–353
Kramer A, Schneider-Mergener J (1998) Methods Mol Biol 187:25–39
Reineke U, Kramer A, Schneider-Mergener J (1999) Curr Top Microbiol Immunol 243:23–36
Weng S, Gu K, Hammond PW, Lohse P, Rise C, Wagner RW, Wright MC, Kuimelis RG (2002) Proteomics 2:48–57
Robinson WH, DiGennaro C, Hueber W, Haab BB, Kamachi M, Dean EJ, Fournel S, Fong D, Genovese MC, Neuman de Vegvar HE, Skriner K, Hirschberg DL, Morris RI, Muller S, Pruijn GJ, van Venrooij WJ, Smolen JS, Brown PO, Steinman L, Utz PL (2002) Nature Med 8:295–301
Mezzasoma L, Bacarese-Hamilton T, Di Cristina M, Rossi R, Bistoni F, Crisanti A (2002) Clin Chem 48:121–130
Gurpide-Madoz J, Wang H, Misek DE, Brichory F, Hanash SM (2001) Proteomics 1:1279–1287
Espejo A, Cote J, Bednarek A, Richard S, Bedford MT (2002) Biochem J 367:697–702
Belov L, de la Vega O, dos Remedios CG, Mulligan SP, Christopherson RI (2001) Cancer Res 61:4483–4489
Yousaf MN, Houseman BT, Mrksich M (2001) Angew Chem Int Ed 40:1093–1096
Paweletz CP, Charboneau L, Bichsel VE, Simone NL, Chen T, Gillespie JW, Emmert-Buck MR, Roth MJ, Petricoin EF, Liotta LA (2001) Oncogene 20:1981–1989
Schweitzer B, Roberts S, Grimwade B, Shao W, Wang M, Fu Q, Shu Q, Laroche I, Zhou Z, Tchernev VT, Christiansen J, Velleca M, Kingsmore SF (2002) Nat Biotechnol 20:359–365
Bobrow MN, Harris TD, Shaughnessy KJ, Litt GJ (1989) J Immunol Methods 125:279–285
Stears RL, Getts RC, Gullans SR (2000) Physiol Genomics 3:93–99
Johnson PJ (2001) Ann New York Acad Sci 945:8-21
Bilban M, Buehler LK, Head S, Desoye G, Quaranta V (2002) Curr Issues Mol Biol 4:57–64
Slonim DK (2002) Nature Genet 32:502–508
Holloway AJ, van Laar RK, Tothill RW, Bowtell DDL (2002) Nature Genet 32:481–489
Xu Y, Selaru FM, Yin J, Zou TT, Shustova V, Mori Y, Sato F, Liu TC, Olaru A, Wang S, Kimos MC, Perry K, Desai K, Greenwald BD, Krasna MJ, Shibata D, Abraham JM, Meltzer SJ (2002) Cancer Res 62:3493–3497
Brown MPS, Grundy WN, Lin D, Cristianini N, Sugnet CW, Furey TS, Manuel Ares M, Haussler D (2000) Proc Natl Acad Sci USA 95:14863–14868
Huang R, Lin Y, Wang CC, Gano J, Lin B, Shi Q, Boynton A, Burke J, Huang R-P (2002) Cancer Res 62:2806–2812
Joos TO, Schrenk M, Hopfl P, Kroger K, Chowdhury U, Stoll D, Schorner D, Durr M, Herick M, Rupp S, Sohn K, Hammerle H (2000) Electrophoresis 21:2641–2650
Neumann L, Wohland T, Whelan RJ, Zare RN, Kobilka BK (2002) ChemBioChem 3:993–998
Mitchell P (2002) Nature Biotechnol 20:225–233
MacBeath GA, Koehler A, Schreiber S (1999) J Am Chem Soc 121:7967–7968
Ge H (2000) Nucleic Acids Res 28:e3
Bussow K, Cahill D, Nietfeld W, Bancroft D, Scherzinger E, Lehrach H, Walter G (1998) Nucleic Acids Res 26:5007–5008
de Wildt RM, Mundy CR, Gorick BD, Tomlinson IM (2000) Nature Biotechnol 18:989–994
Bracci L, Lozzi L, Lelli B, Pini A, Neri P (2001) Biochemistry 40:6611–6619
Kramer A, Volmer-Engert R, Malin R, Reineke U, Schneider-Mergener J (1993) Pept Res 6:314–319
Reineke U, Sabat R, Kramer A, Stigler RD, Seifert M, Michel T, Volk HD (1996) Mol Divers 1:141–148
Alizadeh AA, Ross DT, Perou CM, van de Rijn M (2001) J Pathol 195:41–52
Gygi SP, Rochon Y, Franza BR, Aebersold R (1999) Mol Cell Biol 19:1720–1730
Petricoin EF, Ardekani AM, Hitt BA, Levine PJ, Fusaro VA, Steinberg SM, Mills GB, Simone C, Fishman DA, Kohn EC, Liotta LA (2002) Lancet 359:572–577
Petricoin EF, Zoon KC, Kohn EC, Barrett JC, Liotta LA (2002) Nat Rev Drug Discovery 1:683–695
Cahill DJ (2001) J Immunol Methods 250:81–91
Steiner S, Wahl D, Mangold BLK, Robison R, Raymackers J, Meheus L, Anderson NL, Cordier A (1996) Biochem Biophys Res Commun 218:777–782
Lyons RM, Steiner S, Houy S, Chibout SD, Otto E, Gorziglia M, Kadan M, Kaleko M, Kolopp M (2000) The Toxicologist 54:217
Eberini I, Miller I, Zancan V, Bolego C, Puglisi L, Gemeiner M, Gianazza E (1999) Electrophoresis 20:846–853
VanBogelen RA, Schiller EE, Thomas JD, Neidhardt FC (1999) Electrophoresis 20:2149–2159
Taussig MJ (2001) Comp Func Genomics 2:298–300
Sinskey AJ, Finkelstein SN, Cooper SM (2002) PharmaGenomics 2:20–24
Patterson SD, Aebersold RH (2003) Nature Genet 33:311–323
James P (2002) BioTechniques 33:S4-S13
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kumble, K.D. Protein microarrays: new tools for pharmaceutical development. Anal Bioanal Chem 377, 812–819 (2003). https://doi.org/10.1007/s00216-003-2088-6
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00216-003-2088-6