Continuous Activity Assay for HDAC11 Enabling Reevaluation of HDAC Inhibitors

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F19%3A00519605" target="_blank" >RIV/86652036:_____/19:00519605 - isvavai.cz</a>

Alternative codes found

RIV/68378050:_____/19:00579099

Result on the web

<a href="https://pubs.acs.org/doi/10.1021/acsomega.9b02808" target="_blank" >https://pubs.acs.org/doi/10.1021/acsomega.9b02808</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acsomega.9b02808" target="_blank" >10.1021/acsomega.9b02808</a>

Result language

angličtina

Original language name

Continuous Activity Assay for HDAC11 Enabling Reevaluation of HDAC Inhibitors

Original language description

Histone deacetylase 11 (HDAC11) preferentially removes fatty acid residues from lysine side chains in a peptide or protein environment. Here, we report the development and validation of a continuous fluorescence-based activity assay using an internally quenched TNF alpha-derived peptide derivative as a substrate. The threonine residue in the +1 position was replaced by the quencher amino acid 3'-nitro-L-tyrosine and the fatty acyl moiety substituted by 2-aminobenzoylated 11-aminoundecanoic acid. The resulting peptide substrate enables fluorescence-based direct and continuous readout of HDAC11-mediated amide bond cleavage fully compatible with high-throughput screening formats. The Z'-factor is higher than 0.85 for the 15 mu M substrate concentration, and the signal-to-noise ratio exceeds 150 for 384-well plates. In the absence of NAD(+), this substrate is specific for HDAC 11. Reevaluation of inhibitory data using our novel assay revealed limited potency and selectivity of known HDAC inhibitors, including Elevenostat, a putative HDAC11-specific inhibitor.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10608 - Biochemistry and molecular biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2019

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

ACS Omega

ISSN

2470-1343

e-ISSN

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Volume of the periodical

4

Issue of the periodical within the volume

22

Country of publishing house

US - UNITED STATES

Number of pages

10

Pages from-to

19895-19904

UT code for WoS article

000499133200042

EID of the result in the Scopus database

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