Validation of the Slow Off‐Kinetics of Sirtuin‐Rearranging Ligands (SirReals) by Means of Label‐Free Electrically Switchable Nanolever Technology†

dc.contributor.authorSchiedel, Matthias
dc.contributor.authorDaub, Herwin
dc.contributor.authorItzen, Aymelt
dc.contributor.authorJung, Manfred
dc.date.accessioned2020-10-01
dc.date.available2023-10-11T13:43:27Z
dc.date.created2020
dc.date.issued2020-10-01
dc.description.abstractWe have discovered the sirtuin‐rearranging ligands (SirReals) to be highly potent and selective inhibitors of the NAD+‐dependent lysine deacetylase Sirt2. Using a biotinylated SirReal in combination with biolayer interferometry, we previously observed a slow dissociation rate of the inhibitor–enzyme complex; this had been postulated to be the key to the high affinity and selectivity of SirReals. However, to attach biotin to the SirReal core, we introduced a triazole as a linking moiety; this was shown by X‐ray co‐crystallography to interact with Arg97 of the cofactor binding loop. Herein, we aim to elucidate whether the observed long residence time of the SirReals is induced mainly by triazole incorporation or is an inherent characteristic of the SirReal inhibitor core. We used the novel label‐free switchSENSE® technology, which is based on electrically switchable DNA nanolevers, to prove that the long residence time of the SirReals is indeed caused by the core scaffold.en
dc.format.extent5
dc.identifier.citationChemBioChem 21.8 (2020): 1161-1166. <https://chemistry-europe.onlinelibrary.wiley.com/doi/full/10.1002/cbic.201900527>
dc.identifier.doihttps://doi.org/10.1002/cbic.201900527
dc.identifier.opus-id14616
dc.identifier.urihttps://open.fau.de/handle/openfau/14616
dc.identifier.urnurn:nbn:de:bvb:29-opus4-146164
dc.language.isoen
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0/deed.de
dc.subjectdeacylases
dc.subjectdrug design
dc.subjectepigenetics
dc.subjectprotein modifications
dc.subjectsirtuins
dc.subject.ddcDDC Classification::5 Naturwissenschaften und Mathematik :: 54 Chemie :: 540 Chemie und zugeordnete Wissenschaften
dc.titleValidation of the Slow Off‐Kinetics of Sirtuin‐Rearranging Ligands (SirReals) by Means of Label‐Free Electrically Switchable Nanolever Technology†en
dc.typearticle
dcterms.publisherFriedrich-Alexander-Universität Erlangen-Nürnberg (FAU)
local.date.prevpublished2020-04-24
local.document.pageend1166
local.document.pagestart1161
local.journal.issue8
local.journal.titleChemBioChem
local.journal.volume21
local.sendToDnbfree*
local.subject.fakultaetNaturwissenschaftliche Fakultät
local.subject.gnd-
local.subject.importimport
local.subject.sammlungUniversität Erlangen-Nürnberg / Eingespielte Open Access Artikel / Eingespielte Open Access Artikel 2020
Files
Original bundle
Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
14616_CBIC_CBIC201900527.pdf
Size:
1 MB
Format:
Adobe Portable Document Format
Description: