Book contents
- Frontmatter
- Contents
- Contributors
- Preface
- Section one Overviews
- Chapter 1 Harnessing the Power of Chemistry for Biology and Medicine
- Chapter 2 Exploring Biology with Small Organic Molecules
- Chapter 3 Chemical Proteomics: A Global Study of Protein–Small Molecule Interactions
- Section two Molecules for Chemical Genomics
- Section Three Basics of High-Throughput Screening
- Section Four Chemical Genomics Assays and Screens
- Section five Chemical Genomics and Medicine
- Index
- References
Chapter 3 - Chemical Proteomics: A Global Study of Protein–Small Molecule Interactions
from Section one - Overviews
Published online by Cambridge University Press: 05 June 2012
Edited by
Book contents
- Frontmatter
- Contents
- Contributors
- Preface
- Section one Overviews
- Chapter 1 Harnessing the Power of Chemistry for Biology and Medicine
- Chapter 2 Exploring Biology with Small Organic Molecules
- Chapter 3 Chemical Proteomics: A Global Study of Protein–Small Molecule Interactions
- Section two Molecules for Chemical Genomics
- Section Three Basics of High-Throughput Screening
- Section Four Chemical Genomics Assays and Screens
- Section five Chemical Genomics and Medicine
- Index
- References
Summary
What is chemical proteomics?
Proteins exert their functions through interaction with other proteins or ligands. Therefore, to understand protein function, it is important to analyze protein-protein and protein-ligand interactions. As a result of the completion of the genome sequencing, studies of protein-protein interactions can be conducted on a genome-wide scale. Similarly, biologically active small molecules exert their actions through interaction with their targets, mostly proteins. Thus, the same holds true for analyses of chemicals and proteins. Chemical proteomics is an approach to clarify the biological function of proteins or chemicals through analyses of protein-chemical interactions.
As with genetics, there are two types of chemical proteomics, viz. forward chemical proteomics and reverse chemical proteomics [1]. Although the strategies are different, the primary goals of these two approaches are the same. Both methodologies employ chemicals of interest, so-called bioprobes, at the beginning [2]. The bioprobes with unique biological activities not only lead to drug discovery and development, but they also can be used for investigating many aspects of proteins, such as expression and subcellular localization. If the mode of action of a compound is unknown, we seek to identify the specific cellular targets in cells from the proteome. In forward chemical proteomics, whole-cell lysates are generally screened for interacting proteins, whereas in reverse chemical proteomics, purified or recombinant proteins expressed from the cloned ORFeome (a whole set of open reading frames in an organism) are employed for the target screen. These approaches have both advantages and disadvantages based on the differences in experimental procedures. This section describes their features and typical examples.
- Type
- Chapter
- Information
- Chemical Genomics , pp. 26 - 36Publisher: Cambridge University PressPrint publication year: 2012
References
2006 Integrating forward and reverse proteomics to unravel protein functionProteomics 6 5467Google Scholar
2000 BioprobesTokyoSpringer-Verlag
1999 Paullones, a series of cyclin-dependent kinase inhibitors: synthesis, evaluation of CDK1/cyclin B inhibition, and in vitro antitumor activityJ Med Chem 42 2909Google Scholar
2000 Paullones are potent inhibitors of glycogen synthase kinase-3beta and cyclin-dependent kinase 5/p25Eur J Biochem 267 5983Google Scholar
1989 A receptor for the immunosuppressant FK506 is a peptidyl-prolyl isomeraseNature 341 758Google Scholar
1996 A mammalian histone deacetylase related to the yeast transcriptional regulator Rpd3pScience 272 408Google Scholar
1993 Trapoxin, an antitumor cyclic tetrapeptide, is an irreversible inhibitor of mammalian histone deacetylaseJ Biol Chem 268 22429Google Scholar
1997 The anti-angiogenic agent fumagillin covalently binds and inhibits the methionine aminopeptidase, MetAP-2Proc Natl Acad Sci U S A 94 6099Google Scholar
1997 Methionine aminopeptidase (type 2) is the common target for angiogenesis inhibitors AGM-1470 and ovalicinChem Biol 4 461Google Scholar
1998 Leptomycin B inhibition of signal-mediated nuclear export by direct binding to CRM1Exp Cell Res 242 540Google Scholar
2005 Epolactaene binds human Hsp60 Cys442 resulting in the inhibition of chaperone activityBiochem J 387 835Google Scholar
2005 Inhibition of eukaryotic translation initiation by the marine natural product pateamine AMol Cell 20 709Google Scholar
2006 Chemical genetic identification of the IGF-linked pathway that is mediated by STAT6 and MFP2Chem Biol 13 241Google Scholar
2007 Spliceostatin A targets SF3b and inhibits both splicing and nuclear retention of pre-mRNANat Chem Biol 3 576Google Scholar
1999 Leptomycin B inactivates CRM1/exportin 1 by covalent modification at a cysteine residue in the central conserved regionProc Natl Acad Sci U S A 96 9112Google Scholar
2006 Photo-cross-linked small-molecule microarrays as chemical genomic tools for dissecting protein-ligand interactionsChem Asian J 1 789Google Scholar
1999 Display cloning: functional identification of natural product receptors using cDNA-phage displayChem Biol 6 707Google Scholar
2004 A new curcumin derivative, HBC, interferes with the cell cycle progression of colon cancer cells via antagonization of the Ca2+/calmodulin functionChem Biol 11 1455Google Scholar
2005 Identification and validation of the mitochondrial F1F0-ATPase as the molecular target of the immunomodulatory benzodiazepine Bz-423Chem Biol 12 485Google Scholar
1995 Photocleavable biotin derivatives: a versatile approach for the isolation of biomoleculesProc Natl Acad Sci U S A 92 7590Google Scholar
1981 The purification of avidin and its derivatives on 2-iminobiotin-6-aminohexyl-Sepharose 4BAnal Biochem 114 92Google Scholar
2002 Proteomic profiling of mechanistically distinct enzyme classes using a common chemotypeNat Biotechnol 20 805Google Scholar
1994 A novel biotinylated heterobifunctional cross-linking reagent bearing an aromatic diazirineBioorg Med Chem 2 1367Google Scholar
1996 Synthesis and characterization of a carbene-generating biotinylated N-acetylglucosamine for photoaffinity labeling of beta-(1–>4)-galactosyltransferaseCarbohydr Res 294 95Google Scholar
2007 Splicing factor SF3b as a target of the antitumor natural product pladienolideNat Chem Biol 3 570Google Scholar
2001 Click chemistry: diverse chemical function from a few good reactionsAngew Chem Int Ed Engl 40 2004Google Scholar
1984 1,3-Dipolar Cycloaddition ChemistryNew YorkWiley
2003 Adding amino acids with novel reactivity to the genetic code of J Am Chem Soc 125 11782Google Scholar
2007 Copper-free click chemistry for dynamic in vivo imagingProc Natl Acad Sci U S A 104 16793Google Scholar
2008 Second-generation difluorinated cyclooctynes for copper-free click chemistryJ Am Chem Soc 130 11486Google Scholar
2008 In vivo imaging of membrane-associated glycans in developing zebrafishScience 320 664Google Scholar
2007 Photo-leucine incorporation reveals the target of a cyclodepsipeptide inhibitor of cotranslational translocationJ Am Chem Soc 129 14560Google Scholar
1992 Differential display of eukaryotic messenger RNA by means of the polymerase chain reactionScience 257 967Google Scholar
1997 Difference gel electrophoresis: a single gel method for detecting changes in protein extractsElectrophoresis 18 2071Google Scholar
2001 Validation and development of fluorescence two-dimensional differential gel electrophoresis proteomics technologyProteomics 1 377Google Scholar
2002 In vivo destabilization of dynamic microtubules by HDAC6-mediated deacetylationEmbo J 21 6820Google Scholar
1990 Potent and specific inhibition of mammalian histone deacetylase both in vivo and in vitro by trichostatin AJ Biol Chem 265 17174Google Scholar
2001 Potent histone deacetylase inhibitors built from trichostatin A and cyclic tetrapeptide antibiotics including trapoxinProc Natl Acad Sci U S A 98 87Google Scholar
2008 New insights into chemical biology from ORFeome librariesCurr Opin Chem Biol 12 55Google Scholar
2004 Genome Res 14 2064
2005 Biochemical and genetic analysis of the yeast proteome with a movable ORF collectionGenes Dev 19 2816Google Scholar
2005 Complete set of ORF clones of ASKA library (a complete set of K-12 ORF archive): unique resources for biological researchDNA Res 12 291Google Scholar
2006 ORFeome cloning and global analysis of protein localization in the fission yeast Nat Biotechnol 24 841Google Scholar
2007 hORFeome v3.1: a resource of human open reading frames representing over 10,000 human genesGenomics 89 307Google Scholar
2008 Human protein factory for converting the transcriptome into an in vitro-expressed proteomeNat Methods 5 1011Google Scholar
2010 ViralORFeome: an integrated database to generate a versatile collection of viral ORFsNucleic Acids Res 38 D371Google Scholar
2007 Differential binding of calmodulin-related proteins to their targets revealed through high-density protein microarraysProc Natl Acad Sci U S A 104 4730Google Scholar
2007 Ubiquitination screen using protein microarrays for comprehensive identification of Rsp5 substrates in yeastMol Syst Biol 3 116Google Scholar
2004 Finding new components of the target of rapamycin (TOR) signaling network through chemical genetics and proteome chipsProc Natl Acad Sci U S A 101 16594Google Scholar
1997 Leptomycin B is an inhibitor of nuclear export: inhibition of nucleo-cytoplasmic translocation of the human immunodeficiency virus type 1 (HIV-1) Rev protein and Rev-dependent mRNAChem Biol 4 139Google Scholar
1999 Genomic profiling of drug sensitivities via induced haploinsufficiencyNat Genet 21 278Google Scholar
2004 Discovering modes of action for therapeutic compounds using a genome-wide screen of yeast heterozygotesCell 116 121Google Scholar
2004 Integration of chemical-genetic and genetic interaction data links bioactive compounds to cellular target pathwaysNat Biotechnol 22 62Google Scholar
2004 Chemogenomic profiling: identifying the functional interactions of small molecules in yeastProc Natl Acad Sci U S A 101 793Google Scholar
2006 Exploring the mode-of-action of bioactive compounds by chemical-genetic profiling in yeastCell 126 611Google Scholar
2008 An integrated platform of genomic assays reveals small-molecule bioactivitiesNat Chem Biol 4 498Google Scholar
1999 Functional characterization of the genome by gene deletion and parallel analysisScience 285 901Google Scholar
2010 Marine antifungal theonellamides target 3b-hydroxysterol to activate Rho1 signalingNat Chem Biol 6 519Google Scholar
2011 Microarray-based target identification using drug hypersensitive fission yeast expressing ORFeomeMol Biosyst 7 1463Google Scholar