H5N1 chicken influenza viruses display a high binding affinity for Neu5Acα2-3Galβ1-4(6-HSO3)GlcNAc-containing receptors

AbstractTo characterize differences in the receptor-binding specificity of H5N1 chicken viruses and viruses of aquatic birds, we used a panel of synthetic polyacrylamide (PAA)-based sialylglycopolymers that carried identical terminal Neu5Acα2-3Gal fragments but varied by the structure of the next saccharide residues. A majority of duck viruses irrespective of their HA subtype, bound with the highest affinity to trisaccharide Neu5Acα2-3Galβ1-3GlcNAc, suggesting that these viruses preferentially recognize sialyloligosaccharide receptors with type 1 core (Galβ1-3GlcNAc). Substitution of 6-hydroxyl group of GlcNAc residue of tested sialylglycopolymers by 6-sulfo group had little effect on receptor binding by duck viruses. By contrast, H5N1 chicken and human viruses isolated in 1997 in Hong Kong preferred receptors with type 2 core (Galβ1-4GlcNAcβ) and bound sulfated trisaccharide Neu5Acα2-3Galβ1-4(6-HSO3)GlcNAcβ (6-Su-3′SLN) with the extraordinary high affinity. Another chicken virus, A/FPV/Rostok/34 (H7N1), and several mammalian viruses also displayed an increased affinity for sulfated sialyloligosaccharide receptor. The binding of chicken and mammalian viruses to tracheal epithelial cells of green monkey decreased after treatment of cells with glucosamine-6-sulfatase suggesting the presence of 6-O-Su-3′SLN determinants in the airway epithelium. It remains to be seen whether existence of the 6-O-Su-3′SLN groups in the human airway epithelial cells might facilitate infection of humans with H5N1 chicken viruses

Histochemical detection of expression of binding sites for labelled hyaluronic acid and carrier-immobilized synthetic (histo-blood group trisaccharides) or biochemically purified (ganglioside GM1) glycoligands in nasal polyps and other human lesions including neoplasms

This study is intended to demonstrate the versatility and feasibility of custom-made oligosaccharide- exposing neoglycoconjugates including histo-blood group epitopes in various human lesions, including nasal polyps. The binding of the biotinylated probes was determined on formalin-fixed paraffinembedded sections from archive materials. The general aspects of our results may be interpreted as follows: the neoglycoconjugates used here can readily detect differences in the ability of cells to bind glycan residues in tissue sections, thereby enabling the extent of the binding capacity of various types of human lesions to be compared. Furthermore, the reactivity to glycan may reflect characteristics of the cells and their environment. The investigation into pathological disorders with respect to the binding capacity of these carrierimmobilized mono- or oligosaccharide structures derived from custom-made synthesis or biochemical purification is based on the prospect of translating progress in this field into the establishment of potentially beneficial procedures for medical diagnosis and pathological classification

Solution structure of two xeno-antigens: aGal-LacNAc and aGal-Lewis X

Organ hyperacute rejection, a phenomenon occurring during discordant xenotransplantation, is due to the recognition of an oligosaccharide epitope by human xenoreactive natural antibodies. In addition to the Gal(1-3)Gal(1-4)GlcNAc trisaccharide, a fucosylated structure, Gal-Lewis X, has been shown to be recognized by the antibodies. Both the trisaccharide and the tetrasaccharide have been synthesized by chemical methods. A complete nuclear magnetic resonance characterization of the two compounds has been performed, including the measurements of two-dimensional nuclear Overhauser effect spectroscopy data. Molecular dynamics simulations were run for several ns in the presence of explicit water molecules. The combination of experimental and theoretical approaches revealed the effect of an additional fucose residue on the conformational behavior of the xenoantigen. This branched fucose strongly rigidifies the N-acetyllactosamine. The effect on the Gal(1-3)Gal fragment is less marked. In the presence of fucose, the terminal Gal residue can still adopt two different conformations, but the equilibrium populations are modified

Loading efficiency of doxorubicin into the micelle-like structures formed by function-spacer-lipid constructs self-assembly depends on constructs' functional part

Supramolecular self-assemble systems based on neoglycolipids: Galili-Ad-CMG2-Ad-DOPE, A(type2)-Ad-CMG2-Ad-DOPE are studied here and compared with the well-studied Biotin-CMG2-Ad-DOPE, as well as with their combinations with NH2-CMG2-Ad-DOPE. They are function-spacer-lipid constructs with unique structure that allows them to form micelle-like supramers and be stable, what makes them a potential drug nanocarriers. The structural properties of the obtained supramolecular systems are studied depending on their functional part, and the loading efficiency of doxorubicin into the supramers is determined to reveal the influence of the functional part. The resulting supramers were separated from the unbound molecules by dialysis, the nanoparticles morphology were studied by atomic force microscopy, and the loading efficiency was calculated based on spectrophotometry data. The encapsulation of doxorubicin was confirmed based on changes in the size and shape of the supramers, as well as a decrease in the ratio of unbound molecules. According to the loading efficiency calculations, it was estimated that supramers formed by A(type2)-Ad-CMG2-Ad-DOPE are the most efficient nanocarriers with loading efficiency of 82 %. Supramers formed by NH2-CMG2-Ad-DOPE (no functional part) showed 1.5 times less efficiency. Finally, the least efficient carriers are supramers formed by Biotin-CMG2-Ad-DOPE (14%). © 2021 Institute of Physics Publishing. All rights reserved

Solution structure of two xeno-antigens: α-Gal-LacNAc and α-Gal-Lewis X

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Uncharged P-selectin blockers

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