Samo Guzelj (Avtor), Špela Bizjak (Avtor), Žiga Jakopin (Avtor)

Povzetek

The 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.

Ključne besede

NOD2;desmuramylpeptide;immunostimulant;adamantane;PBMC cytotoxicity;K562;

Podatki

Jezik: Angleški jezik
Leto izida:
Tipologija: 1.01 - Izvirni znanstveni članek
Organizacija: UL FFA - Fakulteta za farmacijo
UDK: 615.4:54:616-097
COBISS: 117643267 Povezava se bo odprla v novem oknu
ISSN: 1948-5875
Št. ogledov: 79
Št. prenosov: 55
Ocena: 0 (0 glasov)
Metapodatki: JSON JSON-RDF JSON-LD TURTLE N-TRIPLES XML RDFA MICRODATA DC-XML DC-RDF RDF

Ostali podatki

Sekundarni jezik: Slovenski jezik
Sekundarne ključne besede: Farmacevtska kemija;Imunomodulatorji;
Vrsta dela (COBISS): Članek v reviji
Strani: str. 1270-1277
Letnik: ǂVol. ǂ13
Zvezek: ǂiss. ǂ8
Čas izdaje: 2022
DOI: 10.1021/acsmedchemlett.2c00121
ID: 16479231