engleski

Synthesis of new amphiphilic triazole derivatives of mannosylated desmuramyl dipeptide

Adjuvants or immunostimulators are substances that are added to vaccines to improve the specific human immune response to a specific antigen. Derivatives of muramyl dipeptide (MDP, N- acetylmuramyl-L-alanyl-D-isoglutamine) as well as desmuramyl dipeptide derivatives (L-Ala-D- isoGln), MDP analogs without the sugar N- acetylmuramyl unit are the well-known adjuvants. [1] Introduction of lipophilic substituent in MDP or L-Ala-D-isoGln pharmacophore can increase its adjuvant activity[2] and binding of mannose to the structure enables mannosylated compounds to interact with lectins specific for mannose. Some of amphiphilic derivatives of DMP have been prepared in our laboratory and their adjuvant activity was tested in vivo (e.g. adamantyl triazole derivative with or without mannose subunit). A further goal of our research is the preparation of various mannosylated desmuramyl dipeptides with different aliphatic subunits linked to α position of D-isoGln through an amide bond via triazole ring (Fig. 1). The protected dipeptide Boc-L-Ala-D-Glu-(OBn) was prepared first as a peptide precursor and then modified successfully in the amidation reaction with various pre-prepared aliphatic (hexadecyl, dodecyl and 2-(adamantan-1-yl)ethyl) 1, 4-disubstituted triazole subunits. The amidation method was also optimized and successfully applied for the introduction of the aliphatic triazole subunits into the structure of the dipeptide. Previously prepared benzyl protected mannose subunit was synthesized from methyl-α-D- mannopyranoside and linked via glycolyl linker to the terminal amino group of alanine. Target amphiphilic derivatives were prepared by removal of protecting group in the last step and they will be tested for their adjuvant activity.

adjuvants ; muramyl dipeptide ; desmuramyl peptide ; triazole, mannose

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