dc.contributor.author | Michel, M | |
dc.contributor.author | Visnes, Torkild | |
dc.contributor.author | Homan, Evert | |
dc.contributor.author | Seashore-Ludlow, Brinton | |
dc.contributor.author | Hedenström, Mattias | |
dc.contributor.author | Wiita, Elisee | |
dc.contributor.author | Vallin, K | |
dc.contributor.author | Paulin, Cynthia BJ | |
dc.contributor.author | Zhang, Jiaxi | |
dc.contributor.author | Wallner, Olov | |
dc.contributor.author | Scobie, Martin | |
dc.contributor.author | Schmidt, A. | |
dc.contributor.author | Jenmalm-Jensen, Annika | |
dc.contributor.author | Warpman Berglund, Ulrika | |
dc.contributor.author | Helleday, Thomas | |
dc.date.accessioned | 2021-10-06T12:13:55Z | |
dc.date.available | 2021-10-06T12:13:55Z | |
dc.date.created | 2019-07-16T11:59:46Z | |
dc.date.issued | 2019 | |
dc.identifier.citation | ACS Omega. 2019, 4 (7), 11642-11656. | en_US |
dc.identifier.issn | 2470-1343 | |
dc.identifier.uri | https://hdl.handle.net/11250/2788142 | |
dc.description.abstract | Due to a polar or even charged binding interface, DNA-binding proteins are considered extraordinarily difficult targets for development of small-molecule ligands and only a handful of proteins have been targeted successfully to date. Recently, however, it has been shown that development of selective and efficient inhibitors of 8-oxoguanine DNA glycosylase is possible. Here, we describe the initial druggability assessment of DNA glycosylases in a computational setting and experimentally investigate several methods to target endonuclease VIII-like 1 (NEIL1) with small-molecule inhibitors. We find that DNA glycosylases exhibit good predicted druggability in both DNA-bound and -unbound states. Furthermore, we find catalytic sites to be highly flexible, allowing for a range of interactions and binding partners. One flexible catalytic site was rationalized for NEIL1 and further investigated experimentally using both a biochemical assay in the presence of DNA and a thermal shift assay in the absence of DNA. | en_US |
dc.language.iso | eng | en_US |
dc.publisher | ACS Publications | en_US |
dc.relation.uri | https://pubs.acs.org/doi/10.1021/acsomega.9b00162 | |
dc.rights | Navngivelse-Ikkekommersiell 4.0 Internasjonal | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc/4.0/deed.no | * |
dc.title | Computational and Experimental Druggability Assessment of Human DNA Glycosylases | en_US |
dc.type | Peer reviewed | en_US |
dc.type | Journal article | en_US |
dc.description.version | publishedVersion | en_US |
dc.rights.holder | ©2019 American Chemical Society | en_US |
dc.source.pagenumber | 11642-11656 | en_US |
dc.source.volume | 4 | en_US |
dc.source.journal | ACS Omega | en_US |
dc.source.issue | 7 | en_US |
dc.identifier.doi | 10.1021/acsomega.9b00162 | |
dc.identifier.cristin | 1711643 | |
cristin.unitcode | 7401,80,1,0 | |
cristin.unitname | Bioteknologi og nanomedisin | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 1 | |