Search: onr:"swepub:oai:DiVA.org:umu-57906" >
Discovery of Ligand...
Discovery of Ligands for ADP-Ribosyltransferases via Docking-Based Virtual Screening
-
- Andersson, C David (author)
- Umeå universitet,Kemiska institutionen
-
- Karlberg, Tobias (author)
- Karolinska Institutet
-
- Ekblad, Torun (author)
- Karolinska Institutet
-
show more...
-
- Lindgren, Anders E G (author)
- Umeå universitet,Kemiska institutionen
-
- Thorsell, Ann-Gerd (author)
- Karolinska Institutet
-
- Spjut, Sara (author)
- Umeå universitet,Kemiska institutionen
-
- Uciechowska, Urszula (author)
- Umeå universitet,Kemiska institutionen
-
- Niemiec, Moritz S (author)
- Umeå universitet,Kemiska institutionen
-
- Wittung-Stafshede, Pernilla (author)
- Umeå universitet,Kemiska institutionen
-
Weigelt, Johan (author)
-
- Elofsson, Mikael (author)
- Umeå universitet,Kemiska institutionen
-
- Schüler, Herwig (author)
- Karolinska Institutet
-
- Linusson, Anna (author)
- Umeå universitet,Kemiska institutionen
-
show less...
-
(creator_code:org_t)
- 2012-08-20
- 2012
- English.
-
In: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 55:17, s. 7706-7718
- Related links:
-
https://urn.kb.se/re...
-
show more...
-
https://doi.org/10.1...
-
http://kipublication...
-
show less...
Abstract
Subject headings
Close
- The diphtheria toxin-like ADP-ribosyltransferases (ARTDs) are an enzyme family that catalyses the transfer of ADP-ribose units onto substrate proteins, using nicotinamide adenine dinucleotide (NAD(+)) as a co-substrate. They have a documented role in chromatin remodelling and DNA repair; and inhibitors of ARTD1 and 2 (PARP1 and 2) are currently in clinical trials for the treatment of cancer. The detailed function of most other ARTDs is still unknown. Using virtual screening we identified small ligands of ARTD7 (PARP15/BAL3) and ARTD8 (PARP14/BAL2). Thermal-shift assays confirmed that 16 compounds, belonging to eight structural classes, bound to ARTD7/ARTD8. Affinity measurements with isothermal titration calorimetry for two isomers of the most promising hit compound confirmed binding in the low micromolar range to ARTD8. Crystal structures showed anchoring of the hits in the nicotinamide pocket. These results form a starting point in the development of chemical tools for the study of the role and function of ARTD7 and ARTD8.
Subject headings
- NATURVETENSKAP -- Kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
-
Andersson, C Dav ...
-
Karlberg, Tobias
-
Ekblad, Torun
-
Lindgren, Anders ...
-
Thorsell, Ann-Ge ...
-
Spjut, Sara
-
show more...
-
Uciechowska, Urs ...
-
Niemiec, Moritz ...
-
Wittung-Stafshed ...
-
Weigelt, Johan
-
Elofsson, Mikael
-
Schüler, Herwig
-
Linusson, Anna
-
show less...
- About the subject
-
- NATURAL SCIENCES
-
NATURAL SCIENCES
-
and Chemical Science ...
- Articles in the publication
-
Journal of Medic ...
- By the university
-
Umeå University
-
Karolinska Institutet