Elena Korchagina

Bio: Elena Korchagina is an academic researcher from Russian Academy of Sciences. The author has contributed to research in topics: Antigen & Synthetic antigen. The author has an hindex of 22, co-authored 66 publications receiving 1554 citations.

Synthesis of polymeric neoglycoconjugates based on N-substituted polyacrylamides.

Abstract: Several types of polymeric glycoconjugates, N-substituted polyacrylamides, have been synthesized by the reaction of activated polymers with omega-aminoalkylglycosides: (i) (carbohydrate-spacer)n-polyacrylamide, 'pseudopolysaccharides'; (ii) (carbohydrate-spacer)n-phosphatidylethanolaminem-polyacrylamide, neoglycolipids, derivatives of phosphatidylethanolamine; (iii) (carbohydrate-spacer)n-biotin-polyacrylamide, biotinylated probes; (iv) (carbohydrate-spacer)n-polyacrylamide-(macroporous glass), affinity sorbents based on macroporous glass, covalently coated with polyacrylamide. An almost quantitative yield in the conjunction reaction makes it possible to insert in the conjugate a predetermined quantity of the ligand(s). Pseudopolysaccharides proved to be a suitable form of antigen for activation of polystyrene and poly(vinyl chloride) plates (ELISA) and nitrocellulose membranes (dot blot), being advantageous over traditional neoglycoproteins. Polyvalent glycolipids insert well in biological membranes: their physical properties, particularly solubility, can be changed in a desired direction. Biotinylated derivatives were used as probes for detection and analysis of lectins.

In vivo immunoadsorption of antipig antibodies in baboons using a specific Gal(alpha)1-3Gal column.

Abstract: The major role of anti-alphaGal antibodies in the hyperacute rejection of pig organs by humans and baboons has been clearly demonstrated. Spacered alpha-galactose disaccharide (Gal(alpha1)-3Gal) hapten was produced by chemical synthesis and covalently attached to a flexible, hydrophilic polymer (PAA), which in turn was covalently coupled to macroporous glass beads, forming an immunoadsorbent that is mechanically and chemically stable and can be sterilized. The extracorporeal immunoadsorption (EIA) of anti-alphaGal antibodies using this column has been investigated in vivo in 3 baboons. In Baboon 1 (which had hyperacutely rejected a pig heart transplant 4 months previously, was not splenectomized, and did not receive any pharmacologic immunosuppression) the levels of anti-alphaGal antibody and antipig IgM and IgG, as well as serum cytotoxicity, fell significantly after each of 3 EIAs but were not eliminated. Serum cytotoxicity, antipig immunoglobulin and anti-alphaGal antibody rose steeply within 24 hr of the final EIA, suggesting that the return of cytotoxicity was associated with anti-alphaGa1 antibody. In Baboons 2 and 3 (which were immunologically naive and splenectomized, and received triple drug immunosuppressive therapy) serum cytotoxicity was totally eliminated and anti-alphaGal antibody and antipig IgM and IgG levels were greatly reduced by courses of EIA. In Baboon 2, cytotoxicity and all antibody levels remained negligible for approximately one week after the final (fourth) daily EIA. In Baboon 3, cytotoxicity and antibody levels were maintained low by intermittent EIA (over a period of 13 days) for almost 3 weeks, although antipig IgM began to rebound 4 days after the final EIA. We conclude that, in an immunosuppressed, splenectomized baboon, repeated EIA using a specific alphaGal disaccharide column will reduce antipig and anti-alphaGal antibody levels and serum cytotoxicity significantly for several days. This reduction in cytotoxicity will almost certainly be sufficient to delay the hyperacute rejection of a transplanted pig organ, but further studies are required to investigate whether it will be sufficient to allow accommodation to develop.

Detection, immunoabsorption, and inhibition of cytotoxic activity of anti‐αGal antibodies using newly developed substances with synthetic Gal α1–3Gal disaccharide epitopes

Abstract: The presence of naturally occurring anti-Galα1–3Gal (anti-αGal) antibodies in human serum is believed to be a major factor in the hyperacute rejection of discordant organ xenografts such as the pig-to-human combination Galα1–3Gal epitopes are expressed on pig tissues and the binding of anti-αGal leads to endothelial cell activation and complement-mediated, hyperacute graft rejection One possible method to overcome this problem is to absorb anti-αGal antibodies from the plasma of the xenograft recipient using a suitable immunoabsorbent or to interfere with their binding to tissues and thus prevent their cytotoxic activity by the intravenous injection of soluble antigen We describe here the use of new synthetic antigens containing the Galα1–3Gal disaccharide (Bdi) epitope Soluble conjugates of the Bdi with polyacrylamide (PAA-Bdi) were used as coating antigens for an anti-αGal ELISA as well as for in vitro inhibition of the cytotoxicity of anti-αGal An immunoabsorbent consisting of PAA-Bdi coupled to macroporous glass (Sorbent Bdi) was tested for absorption of anti-αGal from human serum Anti-αGal IgM, IgG and IgA could be detected by the anti-αGal ELISA and were specifically absorbed by Sorbent Bdi with absorption efficiencies ranging from 70 to 50% for anti-αGal IgG and 60 to 25% for anti-αGal IgM A comparison of the anti-αGal absorption by Sorbent Bdi and rabbit red blood cells revealed a qualitatively (isotype distribution) and quantitatively similar pattern Nonspecific absorption by Sorbent Bdi was low, as detected by the reduction of anti-A trisaccharide antibodies The cytotoxic effect of human serum on pig kidney (PK15) cells was almost totally inhibited by the addition of synthetic B disaccharide or by adsorption of the serum through immunoaffinity columns of PAA-Bdi We conclude that the newly developed, synthetic αGal1–3Gal antigens are suitable for the detection and immunoabsorption or inhibition of anti-αGal antibodies

λ Δ -Models

Abstract: To study the operational behaviour of λ-terms, we will use the denotational (mathematical) approach. A denotational semantics for a language is based on the choice of a space of semantics values, or denotations, where terms are to be interpreted. Choosing a space with nice mathematical properties can help in proving the semantic properties of terms, since to this aim standard mathematical techniques can be used.

Early Alterations of the Receptor-Binding Properties of H1, H2, and H3 Avian Influenza Virus Hemagglutinins after Their Introduction into Mammals

Abstract: Interspecies transmission of influenza A viruses circulating in wild aquatic birds occasionally results in influenza outbreaks in mammals, including humans. To identify early changes in the receptor binding properties of the avian virus hemagglutinin (HA) after interspecies transmission and to determine the amino acid substitutions responsible for these alterations, we studied the HAs of the initial isolates from the human pandemics of 1957 (H2N2) and 1968 (H3N2), the European swine epizootic of 1979 (H1N1), and the seal epizootic of 1992 (H3N3), all of which were caused by the introduction of avian virus HAs into these species. The viruses were assayed for their ability to bind the synthetic sialylglycopolymers 3'SL-PAA and 6'SLN-PAA, which contained, respectively, 3'-sialyllactose (the receptor determinant preferentially recognized by avian influenza viruses) and 6'-sialyl(N-acetyllactosamine) (the receptor determinant for human viruses). Avian and seal viruses bound 6'SLN-PAA very weakly, whereas the earliest available human and swine epidemic viruses bound this polymer with a higher affinity. For the H2 and H3 strains, a single mutation, 226Q-->L, increased binding to 6'SLN-PAA, while among H1 swine viruses, the 190E-->D and 225G-->E mutations in the HA appeared important for the increased affinity of the viruses for 6'SLN-PAA. Amino acid substitutions at positions 190 and 225 with respect to the avian virus consensus sequence are also present in H1 human viruses, including those that circulated in 1918, suggesting that substitutions at these positions are important for the generation of H1 human pandemic strains. These results show that the receptor-binding specificity of the HA is altered early after the transmission of an avian virus to humans and pigs and, therefore, may be a prerequisite for the highly effective replication and spread which characterize epidemic strains.

Chemical biology of the sugar code.

Abstract: A high-density coding system is essential to allow cells to communicate efficiently and swiftly through complex surface interactions. All the structural requirements for forming a wide array of signals with a system of minimal size are met by oligomers of carbohydrates. These molecules surpass amino acids and nucleotides by far in information-storing capacity and serve as ligands in biorecognition processes for the transfer of information. The results of work aiming to reveal the intricate ways in which oligosaccharide determinants of cellular glycoconjugates interact with tissue lectins and thereby trigger multifarious cellular responses (e.g. in adhesion or growth regulation) are teaching amazing lessons about the range of finely tuned activities involved. The ability of enzymes to generate an enormous diversity of biochemical signals is matched by receptor proteins (lectins), which are equally elaborate. The multiformity of lectins ensures accurate signal decoding and transmission. The exquisite refinement of both sides of the protein-carbohydrate recognition system turns the structural complexity of glycans--a demanding but essentially mastered problem for analytical chemistry--into a biochemical virtue. The emerging medical importance of protein-carbohydrate recognition, for example in combating infection and the spread of tumors or in targeting drugs, also explains why this interaction system is no longer below industrial radarscopes. Our review sketches the concept of the sugar code, with a solid description of the historical background. We also place emphasis on a distinctive feature of the code, that is, the potential of a carbohydrate ligand to adopt various defined shapes, each with its own particular ligand properties (differential conformer selection). Proper consideration of the structure and shape of the ligand enables us to envision the chemical design of potent binding partners for a target (in lectin-mediated drug delivery) or ways to block lectins of medical importance (in infection, tumor spread, or inflammation).