Your browser does not allow JavaScript!
JavaScript is necessary for the proper functioning of this website. Please enable JavaScript or use a modern browser.
Open Science Slovenia
Open Science
DiKUL
slv
|
eng
Search
Browse
New in RUL
About RUL
In numbers
Help
Sign in
Novel scaffolds for modulation of NOD2 identified by pharmacophore-based virtual screening
ID
Guzelj, Samo
(
Author
),
ID
Tomašič, Tihomir
(
Author
),
ID
Jakopin, Žiga
(
Author
)
URL - Source URL, Visit
https://www.mdpi.com/2218-273X/12/8/1054
URL - Source URL, Visit
https://www.mdpi.com/2218-273X/12/8/1054
PDF - Presentation file,
Download
(24,71 MB)
MD5: F226A94A9A0B4F7A80AFB676134B32DA
Image galllery
Abstract
Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) is an innate immune pattern recognition receptor responsible for the recognition of bacterial peptidoglycan fragments. Given its central role in the formation of innate and adaptive immune responses, NOD2 represents a valuable target for modulation with agonists and antagonists. A major challenge in the discovery of novel small-molecule NOD2 modulators is the lack of a co-crystallized complex with a ligand, which has limited previous progress to ligand-based design approaches and high-throughput screening campaigns. To that end, a hybrid docking and pharmacophore modeling approach was used to identify key interactions between NOD2 ligands and residues in the putative ligand-binding site. Following docking of previously reported NOD2 ligands to a homology model of human NOD2, a structure-based pharmacophore model was created and used to virtually screen a library of commercially available compounds. Two compounds, 1 and 3, identified as hits by the pharmacophore model, exhibited NOD2 antagonist activity and are the first small-molecule NOD2 modulators identified by virtual screening to date. The newly identified NOD2 antagonist scaffolds represent valuable starting points for further optimization.
Language:
English
Keywords:
antagonist
,
homology modeling
,
NOD2
,
Nucleotide-binding oligomerization
,
pharmacophore modeling
,
virtual screening
Typology:
1.01 - Original Scientific Article
Organization:
FFA - Faculty of Pharmacy
Publication date:
01.01.2022
Year:
2022
Number of pages:
17 str.
Numbering:
Vol. 12, iss. 8, art. 1054
PID:
20.500.12556/RUL-138680-86544121-2823-7222-34ef-8017072a3c05
UDC:
615.4:54:616-006
ISSN on article:
2218-273X
DOI:
10.3390/biom12081054
COBISS.SI-ID:
117616387
Publication date in RUL:
09.08.2022
Views:
520
Downloads:
105
Metadata:
Cite this work
Plain text
BibTeX
EndNote XML
EndNote/Refer
RIS
ABNT
ACM Ref
AMA
APA
Chicago 17th Author-Date
Harvard
IEEE
ISO 690
MLA
Vancouver
:
Copy citation
Share:
Record is a part of a journal
Title:
Biomolecules
Shortened title:
Biomolecules
Publisher:
MDPI
ISSN:
2218-273X
COBISS.SI-ID:
519952921
Licences
License:
CC BY 4.0, Creative Commons Attribution 4.0 International
Link:
http://creativecommons.org/licenses/by/4.0/
Description:
This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
Licensing start date:
09.08.2022
Secondary language
Language:
Slovenian
Keywords:
antagonisti
,
modeliranje homologije
,
NOD2
,
oligomerizacija
,
ki veže nukleotide
,
modeliranje farmakoforja
,
virtualno rešetanje
Projects
Funder:
ARRS - Slovenian Research Agency
Project number:
P1-0208
Name:
Farmacevtska kemija: načrtovanje, sinteza in vrednotenje učinkovin
Funder:
ARRS - Slovenian Research Agency
Project number:
P1-0420
Name:
Napredna imunološka zdravila in celični pristopi v farmaciji
Funder:
ARRS - Slovenian Research Agency
Project number:
J3-9256
Name:
Razvoj agonistov receptorja NOD2 ter dualnih NOD2/TLR7 agonističnih konjugatov kot novih adjuvansov za cepiva
Similar documents
Similar works from RUL:
Similar works from other Slovenian collections:
Back