Samo Guzelj (Avtor),
Sanja Vrbek (Avtor),
Martina Gobec (Avtor),
Stane Pajk (Avtor),
Veronika Klančič (Avtor),
Bram Slütter (Avtor),
Ruža Frkanec (Avtor),
Adela Štimac (Avtor),
Primož Šket (Avtor),
Janez Plavec (Avtor),
Irena Mlinarič-Raščan (Avtor),
Žiga Jakopin (Avtor)
Povzetek
We report on the design, synthesis, and biological evaluation of a series of nucleotide-binding oligomerization-domain-containing protein 2 (NOD2) desmuramylpeptide agonists with improved in vitro and in vivo adjuvant properties. We identified two promising compounds: 68, a potent nanomolar in vitro NOD2 agonist, and the more lipophilic 75, which shows superior adjuvant activity in vivo. Both compounds had immunostimulatory effects on peripheral blood mononuclear cells at the protein and transcriptional levels, and augmented dendritic-cell-mediated activation of T cells, while 75 additionally enhanced the cytotoxic activity of peripheral blood mononuclear cells against malignant cells. The C18 lipophilic tail of 75 is identified as a pivotal structural element that confers in vivo adjuvant activity in conjunction with a liposomal delivery system. Accordingly, liposome-encapsulated 75 showed promising adjuvant activity in mice, surpassing that of muramyl dipeptide, while achieving a more balanced Th1/Th2 immune response, thus highlighting its potential as a vaccine adjuvant.
Ključne besede
reakcijski produkti;reaction products;peptides and proteins;cells;organic compounds;toxicity;
Podatki
Jezik: |
Angleški jezik |
Leto izida: |
2021 |
Tipologija: |
1.01 - Izvirni znanstveni članek |
Organizacija: |
UL FFA - Fakulteta za farmacijo |
UDK: |
615.4:54 |
COBISS: |
64930051
|
ISSN: |
0022-2623 |
Št. ogledov: |
88 |
Št. prenosov: |
66 |
Ocena: |
0 (0 glasov) |
Metapodatki: |
|
Ostali podatki
Sekundarni jezik: |
Slovenski jezik |
Sekundarne ključne besede: |
Farmacevtska kemija;Peptidi;Toksičnost;Organske spojine; |
Vrsta dela (COBISS): |
Članek v reviji |
Strani: |
str. 7809-7838 |
Letnik: |
ǂVol. ǂ64 |
Zvezek: |
ǂiss. ǂ11 |
Čas izdaje: |
2021 |
DOI: |
10.1021/acs.jmedchem.1c00644 |
ID: |
16608079 |