Špela Bizjak (Avtor), Samo Guzelj (Avtor), Petra Kocbek (Avtor), Eveline A. de Vlieger (Avtor), Bram Slütter (Avtor), Žiga Jakopin (Avtor)

Povzetek

Herein we report on the design, synthesis and biological evaluation of a series of nucleotide-binding oligomerization-domain-containing protein 2 (NOD2) desmuramylpeptide agonists. The structural prerequisites that shape both physicochemical and immunomodulatory profiles of desmuramylpeptide NOD2 agonists have been delineated. Within this context, we identified 3, a butyrylated desmuramylpeptide, as a potent in vitro NOD2 agonist (EC50 = 4.6 nM), exhibiting an almost 17-fold enhancement in potency compared to its unsubstituted counterpart 1 (EC50 = 77.0 nM). The novel set of desmuramylpeptides demonstrate unique in vitro immunomodulatory activities. They elicited cytokine production in peripheral blood mononuclear cells (PBMCs), both alone and in conjunction with lipopolysaccharide (LPS). The spermine-decorated 32 also stimulated the LPS-induced cytotoxic activity (2.95-fold) of PBMCs against K562 cancer cells. Notably, the cholesterol-conjugate 26 displayed anti-inflammatory actions, highlighted by its capacity to convert the inflammatory monocyte subset into an anti-inflammatory phenotype. Finally, the eicosapentaenoylated derivative 23 augmented antigen presentation by mouse bone marrow-derived dendritic cells (BMDCs), thus highlighting its potential as a vaccine adjuvant.

Ključne besede

agonists;cells;peptides and proteins;reaction products;toxicity;

Podatki

Jezik: Angleški jezik
Leto izida:
Tipologija: 1.01 - Izvirni znanstveni članek
Organizacija: UL FFA - Fakulteta za farmacijo
UDK: 615.9+615.375
COBISS: 209432835 Povezava se bo odprla v novem oknu
ISSN: 1520-4804
Št. ogledov: 29
Št. prenosov: 4
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: agonisti;celice;peptidi in proteini;reakcijski produkti;Toksičnost;Imunomodulatorji;
Vrsta dela (COBISS): Članek v reviji
Strani: <v tisku>
Letnik: ǂVol. ǂ
Zvezek: ǂno. ǂ
Čas izdaje: 2024
DOI: 10.1021/acs.jmedchem.4c01577
ID: 25266702