Computational and Experimental Druggability Assessment
of Human DNA Glycosylases
Version 2 2019-07-05, 11:05
Version 1 2019-07-04, 08:13
Posted on 2019-07-05 - 11:05
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.
CITE THIS COLLECTION
DataCite
3 Biotech
3D Printing in Medicine
3D Research
3D-Printed Materials and Systems
4OR
AAPG Bulletin
AAPS Open
AAPS PharmSciTech
Abhandlungen aus dem Mathematischen Seminar der Universität Hamburg
ABI Technik (German)
Academic Medicine
Academic Pediatrics
Academic Psychiatry
Academic Questions
Academy of Management Discoveries
Academy of Management Journal
Academy of Management Learning and Education
Academy of Management Perspectives
Academy of Management Proceedings
Academy of Management Review
Michel, Maurice; Visnes, Torkild; Homan, Evert J.; Seashore-Ludlow, Brinton; Hedenström, Mattias; Wiita, Elisée; et al. (2019). Computational and Experimental Druggability Assessment
of Human DNA Glycosylases. ACS Publications. Collection. https://doi.org/10.1021/acsomega.9b00162
or
Select your citation style and then place your mouse over the citation text to select it.
SHARE
Usage metrics
Read the peer-reviewed publication
AUTHORS (15)
MM
Maurice Michel
TV
Torkild Visnes
EH
Evert J. Homan
BS
Brinton Seashore-Ludlow
MH
Mattias Hedenström
EW
Elisée Wiita
KV
Karl Vallin
CP
Cynthia B. J. Paulin
JZ
Jiaxi Zhang
OW
Olov Wallner
MS
Martin Scobie
AS
Andreas Schmidt
AJ
Annika Jenmalm-Jensen
UB
Ulrika Warpman Berglund
TH
Thomas Helleday