A Mild Chemically Cleavable Linker System for Functional Proteomic Applications

Verhelst, Steven H. L.; Fonović, Marko; Bogyo, Matthew

doi:10.1002/ange.200603811

Cited by 126 publications

(23 citation statements)

References 17 publications

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“…Addendum-After submission of this work, two studies describing cleavable probes for functional proteomics were published (30,31). * This work was supported by National Institutes of Health Grants CA087660 (to B. F. C.), CA37393 (to B. R.…”

Section: Figmentioning

confidence: 99%

Assessing Enzyme Activities Using Stable Isotope Labeling and Mass Spectrometry

Everley

Gartner

Haas

et al. 2007

Molecular & Cellular Proteomics

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Section: Figmentioning

confidence: 99%

Assessing Enzyme Activities Using Stable Isotope Labeling and Mass Spectrometry

Everley

Gartner

Haas

et al. 2007

Molecular & Cellular Proteomics

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“…Our linker withstands aqueous, acidic, and basic media (including the widely used Tris buffer), and is resistant towards disulfide-reducing conditions. We thus believe that our linker has some important advantages over the previously reported [5][6][7][8][9] linker systems. Our Figure 2.…”

mentioning

confidence: 96%

“…Examples of such cleavable linkers (CL) are the disulfide linkage, [5] enzymatically (Tev) cleavable, [6] acid-cleavable, [7] diazobenzene-derived (cleavable with Na 2 S 2 O 4 ), [8] and hydrazone-based linkers. [9] An ideal cleavable linker is stable towards the various conditions (acidic, basic, reductive, including generally applied buffer systems) to which the biological sample may be exposed, depending on the nature of the experiment, and can also withstand the reactive (nucleophilic) species that are present in a cell extract.…”

mentioning

confidence: 99%

A Cleavable Linker Based on the Levulinoyl Ester for Activity‐Based Protein Profiling

Geurink

Florea

et al. 2010

Angewandte Chemie

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“…26,27 Similarly, azide moieties that are transferred to substrates from SAM analogues can be used in strain-promoted azide-alkyne cycloaddition (SPAAC) using, for example, dibenzocyclooctyne (DIBO) derivatized fluorophores or biotin handles.…”

mentioning

confidence: 99%

Probing Chromatin-modifying Enzymes with Chemical Tools

Fischle

Schwarzer

2016

ACS Chem. Biol.

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2 Glossary section/Key words:Epigenetics: Inheritance of gene expression profiles independent of changes in DNA sequence or content.Histones: Small, basic proteins that package eukaryotic DNA into chromatin.Nucleosomes: Nucleosome core particles consist of an octamer of histone proteins (2x H2A, H2B, H3, H4) around which 147 bp of DNA are wrapped. Addition of linker DNA of various length and linker histones (H1) makes up the nucleosome as the basic, repeating unit of chromatin. DNA-Methylation:Enzymatic and none-enzymatic modification of DNA bases with methyl-groups.The methylation of C5 of cytosine is most relevant for gene regulation.Histone modifications: Chemical, posttranslational modifications of specific amino acids of histone proteins. The most abundant modifications are acetylation and methylation of the ε-amino group of lysines, methylation of the guanidino group of arginines and phosphorylation of hydroxyl groups in serines and threonines.Chemical probes: Synthetic molecules designed to interact with a protein of interest in order to study its function and activity.Cosubstrate probes: Chemical probes that are derived from the cellular small molecules that donate modifying groups to DNA and histones such as Adenosine triphosphate (ATP), Acetyl coenzyme A (acetyl-CoA) and S-adenosyl methionine (SAM).Substrate profiling: Proteomic approach to define the pool of target proteins of specific modifying enzymes using cosubstrate probes and mass spectrometry. 3 AbstractChromatin is the universal template of genetic information of all eukaryotic organisms. Chemical modifications of the DNA-packaging histone proteins and the DNA bases are crucial signaling events in directing the use and readout of eukaryotic genomes. The enzymes that install and remove these chromatin modifications as well as the proteins that bind these marks govern information that goes beyond the sequence of DNA. Therefore, these so called epigenetic regulators are intensively studied and represent promising drug targets in modern medicine. We summarize and discuss recent advances in the field of chemical biology that have provided chromatin research with sophisticated tools for investigating the composition, activity and target sites of chromatin modifying enzymes and reader proteins. 4In all eukaryotic cells chromatin, the complex of DNA and histone proteins regulates the functional state of the genome by altering condensation states and active recruitment of regulatory factors. The basic structural unit of chromatin is the nucleosome core particle. It consists of a protein core formed by two copies each of the histone proteins H2A, H2B, H3 and H4 with 147 base pairs of DNA wrapped around.1 Nucleosome core particles are connected by linker DNA, which can bind linker histones thereby giving rise to the fundamental repeating unit of chromatin, the nucleosome. Control of different chromatin states is mediated by a multitude of posttranslational modifications (PTMs) of the histone proteins, including methylation, acetylation and phosphorylatio...

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A Mild Chemically Cleavable Linker System for Functional Proteomic Applications

Cited by 126 publications

References 17 publications

Assessing Enzyme Activities Using Stable Isotope Labeling and Mass Spectrometry

Assessing Enzyme Activities Using Stable Isotope Labeling and Mass Spectrometry

A Cleavable Linker Based on the Levulinoyl Ester for Activity‐Based Protein Profiling

Probing Chromatin-modifying Enzymes with Chemical Tools

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