Novel mannosyl derivatives of peptidoglycan monomer: Synthesis and biological evaluation of immunomodulatory properties

Synthesis and Biological Evaluation of New Mannose Derived Immunomodulating Adamantyltripeptides

“…33 Despite numerous synthetic problems encountered in transformations of larger molecules several successful attempts to synthetically modify PGM monomer 1 as a parent compound were made. The previous reports describe the synthesis of PGM modified with Boc-tyrosine, 34 adamant-1-yl, 35 as well as with mannopyranosyl 22 residues. This was possible because the preferential conformation of PGM in aqueous and dimethylsulfoxide solutions showed that the amino group of meso-diaminopimelic acid is exposed and can therefore be manipulated without the interference of other reactive groups.…”

“…As previously described the acids 11 and 12 were prepared in a sequence of steps. 14,22 Commercially available methyl (R) or (S)-3-hydroxy-2-methylpropio-nate was O-mannosylated using benzyl protected mannosyl trichloroacetimidate as a good glycosyl donor and catalytic amounts of Lewis acids as reaction promotors. OGlycosylations gave anomeric mixtures of the corresponding O-glycosides in different ratios.…”

“…In continuation of our interest and research of monosaccharide conjugates, 15 their enzymatic transformations 16−19 and synthesis, 20,21 especially of those with biological activity 8,22 we now report the synthesis of mannose conjugates with admant-1-yl tripeptides 2 and adamant-2-yl tripeptides 3 containing the L-alanyl-D-isoglutamine dipeptide sequence as in PGM and MDP. Furthermore, the study was designed to investigate how mannosylation of adamantyl tripeptides through a chiral spacer of defined configuration (R or S) might affect the immunostimulating activity in mice.…”

“…22,29 The relative quantities of anti-OVA IgG were determined by parallel line assay comparing each serum to monoclonal anti-chicken egg albumin, declared as standard preparation, to which 20,000 arbitrary units per milliliter (AU/mL) were voluntarily assigned.…”

“…23,24 A previous report was also given on the effects of mannosylated PGM on immune reactions in mice and the susceptibility of these derivatives to the enzyme N-acetylmuramyl-L-alanine amidase. 22 Our current study in regard to biological activity of novel mannosylated adamantyltripeptides should provide information on their adjuvant effect on humoral IgG immune response in mice. Ovalbumin was used as a customary antigen for studying the adjuvant effect.…”