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Discovery of desmuramylpeptide NOD2 agonists with single-digit nanomolar potencyGuzelj, Samo ; Janež, Špela, farmacevtka ; Jakopin, ŽigaThe innate immune receptor nucleotide-binding oligomerization-domain-containing protein 2 (NOD2) represents an important target for the development of structurally defined small molecule ... immunomodulatory compounds that have great potential to be used either as vaccine adjuvants or as general immunostimulatory agents. We report here the investigation of the structure–activity relationship of a series of novel desmuramylpeptide NOD2 agonists. Extensive exploration of chemical space culminated in the discovery of a lipophilic adamantane-moiety-featuring compound 40, the first single-digit nanomolar and the most potent NOD2 agonist in its structural class to date. Moreover, 40 acted synergistically with lipopolysaccharide and interferon-γ to induce the production of cytokines in human peripheral blood mononuclear cells and enhance their nonspecific cytotoxic activity against K562 cancer cells. These findings provide initial insight into its immunostimulatory potential, especially when used in combination with other immunopotentiators.Source: ACS Medicinal Chemistry Letters. - ISSN 1948-5875 (Vol. 13, iss. 8, 2022, str. 1270-1277)Type of material - article, component part ; adult, seriousPublish date - 2022Language - englishCOBISS.SI-ID - 117643267
Author
Guzelj, Samo |
Janež, Špela, farmacevtka |
Jakopin, Žiga
Topics
Farmacevtska kemija |
Imunomodulatorji |
NOD2 |
desmuramylpeptide |
immunostimulant |
adamantane |
PBMC cytotoxicity |
K562
Author | Guzelj, Samo ; Janež, Špela, farmacevtka ; Jakopin, Žiga |
Title | Discovery of desmuramylpeptide NOD2 agonists with single-digit nanomolar potency |
Publication date | 2022-07-18 |
COBISS.SI-ID | 117643267 |
Publication version in repository | Publisher's version |
Publication licence | Creative Commons Attribution 4.0 International |
Embargo | Immediate publication for public |
Project(s) from which the publication was funded
Title | Acronym | Project ID | Funder |
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Farmacevtska kemija: načrtovanje, sinteza in vrednotenje učinkovin | P1-0208-2022 |
Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije |
|
Napredna imunološka zdravila in celični pristopi v farmaciji | P1-0420-2022 |
Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije |
|
Razvoj agonistov receptorja NOD2 ter dualnih NOD2/TLR7 agonističnih konjugatov kot novih adjuvansov za cepiva | J3-9256-2018 |
Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije |
Files that belong to the publication
Link |
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https://pubs.acs.org/doi/pdf/10.1021/acsmedchemlett.2c00121 |
https://repozitorij.uni-lj.si/IzpisGradiva.php?id=140527 |
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DRS, in which the journal is indexed
Database name | Field | Year |
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Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
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Guzelj, Samo | 52379 |
Janež, Špela, farmacevtka | 56838 |
Jakopin, Žiga | 26496 |
Source: Personal bibliographies
and: SICRIS
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