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Synthesis and biological evaluation of cholesterol and desmuramyl-peptide conjugates

Project type
Znanstveno-istraživački projekti
University North
Start date
Mar 25th 2024
End date
Mar 31st 2025
Total cost
6461 EUR
More information

Peptidoglycans build the cell walls of bacteria and stimulate the immune system since the human immune system recognizes them as pathogen-associated molecular patterns. The smallest peptidoglycan fragment with pronounced immunostimulatory properties is muramyl-dipeptide (MDP). Research has proven that the desmuramyl-dipeptide part of MDP is the pharmacophore responsible for the activation of the immune response, through the activation of the NOD2 receptor. The modification of desmuramyl-peptide with lipophilic substituents leads to the enhancement of immunostimulatory properties, therefore, within the project, the modification of said desmuramyl-dipeptide with cholesterol is proposed as it represents one of the promising strategies for the preparation of potent immunoadjuvants. Within the proposed research, synthetic methods for the preparation of cholesterol and desmuramyl peptide conjugates will be developed, and the immunostimulating properties of the prepared compounds will be tested in cooperation with scientists from the Faculty of Science University of Zagreb and the Ruđer Bošković Institute. After initial screening with in vitro tests, the adjuvant effect of the most promising compounds will be tested in vivo in a mouse model. The overall stimulation of immunoreaction will also be measured, and the ability of compounds to activate NOD2 and MR receptors will be investigated to elucidate the mechanism of PRR activation. Additionally, the ability to be incorporated into liposomes to enable targeted delivery of compounds will be explored. The conducted study will provide a scientific contribution to the research of modified peptidoglycan fragments to develop potent immunostimulatory.

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