No abstract

Muramyl dipeptide (MDP) is the smallest peptidoglycan fragment able to trigger the immune response. Structural modification of MDP can lead to the preparation of analogs with improved immunostimulant properties, including desmuramyl peptides (DMPs). The aim of this work was to prepare the desmuramyl peptide (L-Ala-D-Glu)-containing adamantyl-triazole moiety and its mannosylated derivative in order to study their immunomodulatory activities in vivo. The adjuvant activity of the prepared compounds was evaluated in a murine model using ovalbumin as an antigen, and compared to the reference adjuvant ManAdDMP. The results showed that the introduction of the lipophilic adamantyl-triazole moiety at the C-terminus of L-Ala-D-Glu contributes to the immunostimulant activity of DMP, and that mannosylation of DMP modified with adamantyl-triazole causes the amplification of its immunostimulant activity.

a Bacterial adhesion, mediated through interaction of bacterial lectins with carbohydrate structures presented on the surface of the host cells, is a prerequisite for infection. Anti-adhesion therapy, based on the inhibition of lectins by suitable carbohydrates, has been considered as a weapon for the combat of microbial diseases. Structural alteration of aglycon portions of mannose derivatives strongly influences their inhibitory potency toward type 1 fimbriated Escherichia coli. Thus several conjugates of mannosecontaining ferrocene aglycon moieties were synthesized and tested. The novel ferrocene conjugates 10, 12 and 14 were obtained by esterification of O-mannosylated propionic acid 1 with ferrocene alcohols R-Fn-(CH 2 ) n -OH (Fn = 1,1'-ferrocenylene; 2, n = 1, R = COOMe; 7, n = 1, R = NHBoc; 8, n = 2, R = H) in the presence of Boc 2 O/DMAP with subsequent debenzylation of the intermediate O-protected esters. Performed hemagglutination inhibitory tests showed that the examined bioorganometallics exhibit better inhibitory activity than known inhibitor methyl a-D-mannoside. Thus ferrocene-mannose conjugate 14 with the dimethylene spacer between ferrocene core and chiral linker displayed the best inhibitory efficiency.

Structural alterations of the aglycon portions of α-mannosides influence their inhibitory potency toward type 1-fimbriated Escherichia coli. The aim of our work was to prepare and explore inhibitory properties of novel mannosylated N-aryl-substituted 3-hydroxypyridine-4-ones because they possess needed structural characteristics as possible FimH antagonists. Hemagglutination inhibitory tests showed that the examined 3-hydroxypyridine-4-one α-mannosides exhibited better inhibitory activity than methyl α-d-mannopyranoside used as a reference compound. Molecular modeling studies revealed the specific interactions responsible for the observed binding activities toward the mannose-specific FimH lectin. The activity depends on the substituent in p-position on the aglycon aromatic ring.

Escherichia coli adhesion to the bladder epithelium is mediated through recognition of the tissue-surface mannosylated proteins with bacterial lectin FimH. The inhibition of this recognition-dependent interaction has been recognized as a promising strategy for the development of an anti-adhesion therapy. Mannosides with either aryl-or elongated alkyl-functionalized aglycon portions have been shown to be potent inhibitors of FimH-mediated adhesion. Thus, we have synthesized four mannose-based bioorganometallics containing an extended alkyl chain between sugar and ferrocene components connected via ester linkage (14 (n = 4) and 15 (n = 5)) or amide linkage (18 (n = 3) and 19 (n = 4)). The novel bioconjugates were characterized using infrared and NMR ( 1 H, 13 C, COSY, NOESY, HSQC, HMBC) spectroscopies, electrospray ionization mass spectrometry and high-resolution mass spectrometry. Hemagglutination inhibitory assay of the novel bioorganometallics revealed an enhanced inhibitory potential in comparison to methyl α-D-mannoside. Thereby, the bioconjugate 19 exhibited a twofold increase in inhibitory activity compared with 14, 15 and 18.