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  • Structural fine-tuning of desmuramylpeptide NOD2 agonists defines their in vivo adjuvant activity
    Guzelj, Samo ...
    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.
    Source: Journal of medicinal chemistry. - ISSN 0022-2623 (Vol. 64, iss. 11, 2021, str. 7809-7838)
    Type of material - article, component part
    Publish date - 2021
    Language - english
    COBISS.SI-ID - 64930051

    Link(s):

    https://pubs.acs.org/doi/10.1021/acs.jmedchem.1c00644
    Repository of the University of Ljubljana – RUL
    DOI

source: Journal of medicinal chemistry. - ISSN 0022-2623 (Vol. 64, iss. 11, 2021, str. 7809-7838)

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