Protein microarrays: new tools for pharmaceutical development

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.

[1]  T. Harris,et al.  Catalyzed reporter deposition, a novel method of signal amplification. Application to immunoassays. , 1989, Journal of immunological methods.

[2]  Stuart L. Schreiber,et al.  Printing Small Molecules as Microarrays and Detecting Protein−Ligand Interactions en Masse , 1999 .

[3]  R. Zare,et al.  Functional Immobilization of a Ligand‐Activated G‐Protein‐Coupled Receptor , 2002, Chembiochem : a European journal of chemical biology.

[4]  E. Petricoin,et al.  Use of proteomic patterns in serum to identify ovarian cancer , 2002, The Lancet.

[5]  S. Wölfl,et al.  Preparation of DNA and protein micro arrays on glass slides coated with an agarose film. , 2000, Nucleic acids research.

[6]  S. Schreiber,et al.  Printing proteins as microarrays for high-throughput function determination. , 2000, Science.

[7]  A. Pini,et al.  Mimotopes of the nicotinic receptor binding site selected by a combinatorial peptide library. , 2001, Biochemistry.

[8]  R. Aebersold,et al.  Proteomics: the first decade and beyond , 2003, Nature Genetics.

[9]  D. Gerhold,et al.  DNA chips: promising toys have become powerful tools. , 1999, Trends in biochemical sciences.

[10]  M. Mrksich,et al.  Peptide chips for the quantitative evaluation of protein kinase activity , 2002, Nature Biotechnology.

[11]  K. Lam,et al.  Peptide and small molecule microarray for high throughput cell adhesion and functional assays. , 2001, Bioconjugate chemistry.

[12]  R. Kaiser,et al.  Phenylboronic acid-salicylhydroxamic acid bioconjugates. 1. A novel boronic acid complex for protein immobilization. , 2001, Bioconjugate chemistry.

[13]  B. Stillman,et al.  FAST slides: a novel surface for microarrays. , 2000, BioTechniques.

[14]  T. Barrette,et al.  Profiling of cancer cells using protein microarrays: discovery of novel radiation-regulated proteins. , 2001, Cancer research.

[15]  D. Slonim From patterns to pathways: gene expression data analysis comes of age , 2002, Nature Genetics.

[16]  Ruo-Pan Huang,et al.  Connexin 43 suppresses human glioblastoma cell growth by down-regulation of monocyte chemotactic protein 1, as discovered using protein array technology. , 2002, Cancer research.

[17]  Lucy J. Holt,et al.  The use of recombinant antibodies in proteomics. , 2000, Current opinion in biotechnology.

[18]  M. J. Cunningham,et al.  Genomics and proteomics: the new millennium of drug discovery and development. , 2000, Journal of pharmacological and toxicological methods.

[19]  Jean Philippe Stephan,et al.  Development of a frozen cell array as a high-throughput approach for cell-based analysis. , 2002, The American journal of pathology.

[20]  S. Orencole,et al.  Array-based ELISAs for high-throughput analysis of human cytokines. , 2001, BioTechniques.

[21]  Dieter Stoll,et al.  A microarray enzyme‐linked immunosorbent assay for autoimmune diagnostics , 2000, Electrophoresis.

[22]  I. Miller,et al.  Proteins of rat serum IV. Time‐course of acute‐phase protein expression and its modulation by indomethacine , 1999, Electrophoresis.

[23]  N. Anderson,et al.  Induction of the adipose differentiation-related protein in liver of etomoxir-treated rats. , 1996, Biochemical and biophysical research communications.

[24]  Ye Fang,et al.  G‐Protein‐Coupled Receptor Microarrays , 2002, Chembiochem : a European journal of chemical biology.

[25]  A. Mirzabekov,et al.  Manual manufacturing of oligonucleotide, DNA, and protein microchips. , 1997, Analytical biochemistry.

[26]  J. Seilhamer,et al.  A comparison of selected mRNA and protein abundances in human liver , 1997, Electrophoresis.

[27]  S. Kingsmore,et al.  Multiplexed protein profiling on microarrays by rolling-circle amplification , 2002, Nature Biotechnology.

[28]  Rick Wiese,et al.  Simultaneous analysis of eight human Th1/Th2 cytokines using microarrays. , 2002, JIM - Journal of Immunological Methods.

[29]  E. Petricoin,et al.  Reverse phase protein microarrays which capture disease progression show activation of pro-survival pathways at the cancer invasion front , 2001, Oncogene.

[30]  Jens Schneider-Mergener,et al.  Mapping protein-protein contact sites using cellulose-bound peptide scans , 1996, Molecular Diversity.

[31]  S. Gygi,et al.  Correlation between Protein and mRNA Abundance in Yeast , 1999, Molecular and Cellular Biology.

[32]  P. Brown,et al.  Exploring the metabolic and genetic control of gene expression on a genomic scale. , 1997, Science.

[33]  P. Mitchell A perspective on protein microarrays , 2002, Nature Biotechnology.

[34]  Ash A. Alizadeh,et al.  Towards a novel classification of human malignancies based on gene expression patterns , 2001, The Journal of pathology.

[35]  L J Lesko,et al.  Pharmacogenomic-guided drug development: regulatory perspective , 2002, The Pharmacogenomics Journal.

[36]  Milan Mrksich,et al.  Turning On Cell Migration with Electroactive Substrates , 2001 .

[37]  I. Tomlinson,et al.  Antibody arrays for high-throughput screening of antibody–antigen interactions , 2000, Nature Biotechnology.

[38]  H. Lehrach,et al.  A method for global protein expression and antibody screening on high-density filters of an arrayed cDNA library. , 1998, Nucleic acids research.

[39]  M. Gerstein,et al.  Analysis of yeast protein kinases using protein chips , 2000, Nature Genetics.

[40]  D. Cahill,et al.  Protein and antibody arrays and their medical applications. , 2001, Journal of immunological methods.

[41]  Michael J. Taussig,et al.  Protein Arrays: Issues to Be Addressed , 2001, Comparative and functional genomics.

[42]  Andrea Crisanti,et al.  Antigen microarrays for serodiagnosis of infectious diseases. , 2002, Clinical chemistry.

[43]  F. Neidhardt,et al.  Diagnosis of cellular states of microbial organisms using proteomics , 1999, Electrophoresis.

[44]  A. Mirzabekov,et al.  Protein microchips: use for immunoassay and enzymatic reactions. , 2000, Analytical biochemistry.

[45]  P. Brown,et al.  Autoantigen microarrays for multiplex characterization of autoantibody responses , 2002, Nature Medicine.

[46]  H. Ge,et al.  UPA, a universal protein array system for quantitative detection of protein-protein, protein-DNA, protein-RNA and protein-ligand interactions. , 2000, Nucleic acids research.

[47]  L. K. Buehler,et al.  Normalizing DNA microarray data. , 2002, Current issues in molecular biology.

[48]  Andrew J. Holloway,et al.  Options available—from start to finish—for obtaining data from DNA microarrays II , 2002, Nature Genetics.

[49]  R. Christopherson,et al.  Immunophenotyping of leukemias using a cluster of differentiation antibody microarray. , 2001, Cancer research.

[50]  Jing Yin,et al.  Artificial neural networks and gene filtering distinguish between global gene expression profiles of Barrett's esophagus and esophageal cancer. , 2002, Cancer research.

[51]  Jocelyn Côté,et al.  A protein-domain microarray identifies novel protein-protein interactions. , 2002, The Biochemical journal.

[52]  L. Hood,et al.  Complementary Profiling of Gene Expression at the Transcriptome and Proteome Levels in Saccharomyces cerevisiae*S , 2002, Molecular & Cellular Proteomics.

[53]  E. Petricoin,et al.  Clinical proteomics: translating benchside promise into bedside reality , 2002, Nature Reviews Drug Discovery.

[54]  A. Kramer,et al.  Antigen sequence- and library-based mapping of linear and discontinuous protein-protein-interaction sites by spot synthesis. , 1999, Current topics in microbiology and immunology.