engleski

Using click chemistry for the synthesis of peptidomimetic immunomodulators

Click chemistry refers to fast reactions that give very high chemical yields, use easily removable solvents and mild conditions while byproducts are easily removable as well. Staudinger ligation, copper free and copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) have been increasingly used for fluorescent labeling of biomolecules as well as for the synthesis of small biologically active compounds. Peptidogycans are polymeric components of bacterial cell walls and their monomers stimulate strong immune response. It has been shown that a minimal structural unit of peptidoglycan monomer showing a significant adjuvant activity is muramyldipeptide (MurNAc-L-Ala-D-isoGln, MDP). The aim of this work was the synthesis of mannosylated derivatives of desmuramylpeptides, MDP analogues lacking the original carbohydrate moiety, for further biological evaluation. Mannose moiety serves for targeting the mannose receptors on surface of the immune cells thereby enhancing the specificity of interactions with the cells thus affecting the type of immune response. In order to improve the lipophilicity of mannosylated desmuramyldipeptides, some of which have been previously shown to improve the pharmacological properties of MDP, the peptide part was conjugated with the adamantyl moiety over a triazole ring. Adamantyl substituted triazoles were prepared via CuAAC, conjugated with desmuramyldipeptides and linked to mannose via different short linkers to improve flexibility and accessibility of mannose towards mannose receptors.

chemistry ; peptidomimetics ; immunomodulators ; synthesis

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