Laboratory of Carbohydrates
The Laboratory is engaged in the synthesis of oligosaccharides, glycoconjugates and self-assembling peptides/glycopeptides, design of glycoarrays and glycolandscapes, study of carbohydrate-protein interactions, characterization of specificity of mammalian and bacterial lectins, study of natural anti-glycan antibodies.
Researchers of the Laboratory together with Consortium for Functional Glycomics have developed a glycan microarray (printed glycan array, PGA) – a multi-antigen microchip; due to the presence of tumor-specific markers (glycans) it allows for prognosis, diagnosis and monitoring of cancer at a new level. Now it is possible to use it both in basic research and in the development of diagnostic approaches, first of all oncological and reproductive system diseases.
Booming interest in the self-assembly of small molecules is due to the ability to use them in design of nanomaterials with individual properties and molecular devices. To gather nanomaterials and devices we use simple molecules consisting almost exclusively of oligoglycine; the chains are organized in a star-like fashion. Oligoglycines are capable of forming supramers due to hydrogen bonds. In supramers of (Glycosyl-S)n type, the S-fragment provides the assembly, and the carbohydrate part provides both biological activity and water solubility. Click here for details.
Synthesis of oligosaccharides and glycoconjugates
The Laboratory is engaged in the synthesis of oligosaccharides and glycoconjugates, the universal instruments for various biochemical and immunological studies of all types of carbohydrate-binding proteins. Details are here and here.
Modification of the cell surface (glyco-landscaping)
The Laboratory is engaged in studying the transfer of glycolipids between cells, as well as the development of synthetic glycolipids (and similarly constructed lipophilic peptides) capable of insertion into almost any cell (animal cells, bacteria, membrane viruses). Modification of erythrocytes allows to identify antibodies (in practical, diagnostics purposes) by the simplest possible method – the agglutination.
"Painting" of cancer cells with synthetic glycolipids promised to be new therapeutic approach, it based on the initiation of an immune antitumor response: injection of the glycolipid into the tumor leads to an immediate immune attack with pre-existing natural antibodies directed to the glycan of this glycolipid. We identified a number of natural antibodies that specifically bind and destroy the cells of breast cancer. Click here and here for details.
Also, the Laboratory is engaged in development of vaccines based on dendritic cells.
The Laboratory collaborates with Institute’s departments and also with the Blokhin Cancer Research Center, the Kulakov Scientific Center of Obstetrics, Gynecology and Perinatology, the Bellvitge University Hospital (Barcelona, Spain), the Institute of Health Research of the University of Nantes (France), the Auckland University of Technology (New Zealand), the Institute for Glycomics of the Griffith University (Australia), the University of Basel (Switzerland), the Masaryk University Central European Institute of Technology (Czech Republic) etc.
The Laboratory of Carbohydrates was organized in 1988, it became a natural continuation of the direction laid by academician N. Kochetkov and then Professor A. Khorlin (“Laboratory of glycoproteins and mixed biopolymers”) in the Institute.
- Synthesis of oligosaccharides and glycoconjugates, self-associating peptides and glycopeptides;
- Design of diagnostic glycoarray;
- Study of carbohydrate-protein interactions;
- Natural antibodies to carbohydrates, B1 cell immunity.
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Glycan specificity of galectin-1 depends on its modular organization, despite the identity of the modules
The variants of recombinant galectin-1 where carbohydrate-binding domains are organized differently from the native protein were studied here. The native protein has two domains are connected from head to tail in conjunction. We also have studied two-domain variants but with additional short and long spacer and four-domain ones. It turned out that two-domain constructs selectively lose the ability to bind some canonical glycans-ligands of galectin-1. The same was observed in case of galectin-3.
Study of human natural antibodies glycocalix furing the fiest year of life revealed three aspects that are contradictory to current knowledge
Not all maternal IgG are detected in babies; dome specificities are absent till the age of 12 months. Thus, a mechanism preventing their migration through placenta possibly exists.
Babies fed by breast milk have less anti-glycan antibodies. In other words ‘unnatural’ feeding is accompanied by too early appearing of antibodies
It has been considered that at the age of 2 months maternal IgG slready are absent in babies. We observe that their level st this age is only two times lower, i.e. it rests considerable.
Supramers on the base of amphiphillic molecules lipid-oligopeptide-biotin
In collaboration with Laboratory of biomolecular modeling,  Laboratory of Molecular Biophysics
It was found that oligopeptides with terminal lipid and biotin fragments are able to form micelle-like supramers (globules) in an aqueous solution. Using optical spectroscopy, atomic-force and electron microscopy, as well as small-angle X-ray scattering and computer simulation, it was shown that the globules are very uniform in size (about 14.6 nm). It was found that globules have the core/shell structure. The core contains lipid and part (up to 90%) of the biotin fragments. The polar oligopeptide spacer folds back upon itself and predominantly places the biotin reside inside the globule. But the part ( <10%) of biotin residues is exposed outside, and can be used for the selective attachment of specified molecules. Micelle-like supramers containing compounds that are natural to a living organism can become the basis for new types of carriers for targeted drug delivery.
Influence of stabilizing components in the lipid bilayer on the integrity of antitumor liposomes loaded with lipophilic prodrug, in human serum
In collaboration with Laboratory of lipid chemistry
We compared the effect of different amphiphiles in lipid bilayer on the integrity of 100-nm-liposomes loaded with lipophilic prodrug of chemotherapeutic agent melphalan, in human serum. Using fluorescence methods phosphatidylinositol was shown to protect fluid phase lipid bilayer based upon egg phosphatidylcholine at least for 4 hours, while ganglioside GM1 or a conjugate of carboxylated oligoglycine with phosphatidylethanolamine up to 24 hours. At the same time, polyethylene glycol (2000 Da) conjugated with dipalmitoylphosphatidylethanolamine (PEG-lipid) promoted degradation of liposomes, so that lipids began to exit fluid phase membrane, while gel phase membrane with less than 10 mol % of PEG-lipid was immediately cracked. Cholesterol-containing bilayers of condenced liquid ordered phase, supplemented with sufficient amounts of the PEG-lipid, showed good stability in serum. The above effects should be accounted when using lipophilic conjugates of PEG in the composition of supramolecular drug delivery systems devoid of covalent bonds, such as liposomes, lipid nanospheres, or micelles.
- (2018). Influence of stabilizing components on the integrity of antitumor liposomes loaded with lipophilic prodrug in the bilayer. Colloids Surf B Biointerfaces 166, 45–53