Rosana Ribić

Surface modified liposomes by mannosylated conjugates anchored via the adamantyl moiety in the lipid bilayer

The aim of the present study was to encapsulate mannosylated 1-aminoadamantane and mannosylated adamantyltripeptides, namely [(2R)-N-(adamant-1-yl)-3-(α,β-d-mannopyranosyloxy)-2-methylpropanamide and (2R)-N-[3-(α-d-mannopyranosyloxy)-2-methylpropanoyl]-d,l-(adamant-2-yl)glycyl-l-alanyl-d-isoglutamine] in liposomes. The characterization of liposomes, size and surface morphology was performed using dynamic light scattering (DLS) and atomic force microscopy (AFM). The results have revealed that the encapsulation of examined compounds changes the size and surface of liposomes. After the concanavalin A (ConA) was added to the liposome preparation, increase in liposome size and their aggregation has been observed. The enlargement of liposomes was ascribed to the specific binding of the ConA to the mannose present on the surface of the prepared liposomes. Thus, it has been shown that the adamantyl moiety from mannosylated 1-aminoadamantane and mannosylated adamantyltripeptides can be used as an anchor in the lipid bilayer for carbohydrate moiety exposed on the liposome surface.

Synthesis and immunostimulating properties of novel adamant-1-yl tripeptides.

The aim of this work was to prepare L‐ and D‐(adamant‐1‐yl)‐Gly‐L‐Ala‐D‐isoGln peptides in order to study their adjuvant (immunostimulating) activities. Adjuvant activity of adamant‐1‐yl tripeptides was tested in the mouse model using ovalbumin as an antigen and in comparison to the peptidoglycan monomer (PGM; β‐D‐GlcNAc‐(1→4)‐D‐MurNAc‐L‐Ala‐D‐isoGln‐mesoDAP(εNH2)‐D‐Ala‐D‐Ala) and structurally related adamant‐2‐yl tripeptides.

Mannosylated N-Aryl Substituted 3-Hydroxypyridine-4-Ones: Synthesis, Hemagglutination Inhibitory Properties, and Molecular Modeling

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.

Influence of mannosylation on immunostimulating activity of adamant-1-yl tripeptide.

The mannosylated derivative of adamant‐1‐yl tripeptide (D‐(Ad‐1‐yl)Gly‐L‐Ala‐D‐isoGln) was prepared to study the effects of mannosylation on adjuvant (immunostimulating) activity. Mannosylated adamant‐1‐yl tripeptide (Man‐OCH2CH(Me)CO‐D‐(Ad‐1‐yl)Gly‐L‐Ala‐D‐isoGln) is a non‐pyrogenic, H2O‐soluble, and non‐toxic compound. Adjuvant activity of mannosylated adamantyl tripeptide was tested in the mouse model with ovalbumin as an antigen and in comparison to the parent tripeptide and peptidoglycan monomer (PGM, β‐D‐GlcNAc‐(1→4)‐D‐MurNAc‐L‐Ala‐D‐isoGln‐mesoDAP(εNH2)‐D‐Ala‐D‐Ala), a well‐known effective adjuvant. The mannosylation of adamantyl tripeptide caused the amplification of its immunostimulating activity in such a way that it was comparable to that of PGM.

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

The aim of this work was to prepare mannosyl derivatives of peptidoglycan monomer (PGM, beta-d-GlcNAc-(1-->4)-d-MurNAc-l-Ala-d-isoGln-mesoDAP(epsilonNH(2))-d-Ala-d-Ala) in order to study the effects of mannosylation on adjuvant (immunostimulating) activity. Novel Man-OCH(2)CH(CH(3))CO-PGM isomers were substrates for N-acetylmuramyl-l-alanine amidase, like the parent PGM molecule. Adjuvant activity of Man-OCH(2)CH(CH(3))CO-PGM was tested in the mouse model using ovalbumin as an antigen.