326 research outputs found

    Классификация моделей комплексной оценки финансового состояния предприятия

    Get PDF
    There is an urgent need to develop reliable strategies for the rapid assembly of complex oligosaccharides. This paper presents a set of strategically selected orthogonal protecting groups, glycosyl donors modified by a (S)-phenylthiomethylbenzyl ether at C-2, and a glycosyl acceptor containing a fluorous tag, which makes it possible to rapidly prepare complex branched oligosaccharides of biological importance. The C-2 auxiliary controlled the 1,2-cis anomeric selectivity of the various galactosylations. The orthogonal protecting groups, 2-naphthylmethyl ether (Nap) and levulinic ester (Lev), made it possible to generate glycosyl acceptors and allowed the installation of a crowded branching point. After the glycosylations, the chiral auxiliary could be removed using acidic conditions, which was compatible with the presence of the orthogonal protecting groups Lev and Nap, thereby allowing the efficient installation of 1,2-linked glycosides. The light fluorous tag made it possible to purify the compounds by a simple filtration method using silica gel modified by fluorocarbons. The set of building blocks was successfully employed for the preparation of the carbohydrate moiety of the GPI anchor of Trypanosoma brucei, which is a parasite that causes sleeping sickness in humans and similar diseases in domestic animals

    Chemoenzymatic Synthesis of Heparan Sulfate Oligosaccharides having a Domain Structure

    Get PDF
    Heparan sulfate (HS) has a domain structure in which regions that are modified by epimerization and sulfonation (NS domains) are interspersed by unmodified fragments (NA domains). There is data to support that domain organization of HS can regulate binding of proteins, however, such model has been difficult to probe. Here, we report a chemoenzymatic methodology that can provide HS oligosaccharides composed of two or more NS domains separated by NA domains of different length. It is based on the chemical synthesis of a HS oligosaccharide that enzymatically was extended by various GlcA-GlcNAc units and terminated in GlcNAc having an azido moiety at C-6 position. HS oligosaccharides having an azide and alkyne moiety could be assembled by copper catalyzed alkyne-azide cycloaddition to give compounds having various NS domains separated by unsulfonated regions. Competition binding studies showed that the length of an NA domain modulates the binding of the chemokines CCL5 and CXCL8

    Guillain-Barre syndrome:expanding the concept of molecular mimicry

    Get PDF
    Guillain-Barre syndrome (GBS) is a rapidly progressive, monophasic, and potentially devastating immune-mediated neuropathy in humans. Preceding infections trigger the production of cross-reactive antibodies against gangliosides concentrated in human peripheral nerves. GBS is elicited by at least five distinct common bacterial and viral pathogens, speaking to the notion of polymicrobial disease causation. This opinion emphasizes that GBS is the best-supported example of true molecular mimicry at the B cell level. Moreover, we argue that mechanistically, single and multiplexed microbial carbohydrate epitopes induce IgM, IgA, and IgG subclasses in ways that challenge the classic concept of GBS. Finally, we discuss how GBS can be exemplary for driving innovation in diagnostics and immunotherapy for other antibody-driven neurological diseases

    Метод измерения ударной вязкости как критерий оценки качества углеграфитовых материалов

    Get PDF
    Рассмотрены результаты внедрения метода измерения ударной вязкости в условиях ОАО «Укрграфит». НТУУ «КПИ» и ОАО «Укрграфит» cовместно выполнили работу по адаптации стандартного метода измерения ударной вязкости к испытанию графитированных материалов. Подобран размер образца, выполнен проект и изготовлен маятник для копра МК-5. Проведено измерение ударной вязкости материалов графитированных электродов различных марок. Установлена зависимость ударной вязкости от критерия термостойкости материала ЭГСП. Выявлена прямая пропорциональность между этими параметрами. В результате ряда технологических приемов удалось добиться повышения ударной вязкости материалов (%): ЭГСП – на 7; ниппеля – 20.Розглянуто результати впровадження методу вимірювання ударної в’язкості в умовах ВАТ «Укрграфіт». НТУУ «КПІ» і ВАТ «Укрграфіт» спільно виконали роботу з адаптації стандартного методу виміру ударної в’язкості до випробування графітованих матеріалів. Підібрано розмір зразка, виконано проект і виготовлено маятник для копра МК-5. Проведено вимірювання ударної в’язкості матеріалів графітованих електродів різних марок. Встановлено залежність ударної в’язкості від критерію термостійкості матеріалу ЕГСП. Виявлено пряму пропорційність між цими параметрами. В результаті ряду технологічних прийомів вдалося досягти підвищення ударної в’язкості матеріалів (%): ЕГСП – на 7; ніпеля – 20.The results of introduction of impact strength measurement method at JSC «Ukrgrafit» are described. Ukrainian UST «KPI» and JSC «Ukrgrafit» in common performed work on adaptation of standard impact strength measurement method to graphite material tests. The size of a sample was selected, the design was performed and a pendulum for impact testing machine MK-5 was manufactured. Impact strength measurement for various grade graphite electrode materials was performed. Impact strength depends on the conditions of manufacturing and raw material used. Dependence of impact strength on the heat resistance criterion of EGSP material was established. Direct proportionality between those parameters was revealed. As a result of a number of techniques better impact strength was achieved (%): for EGSP material – by 7; for nipple material – 20

    Ценовая стратегия устойчивого развития предприятий зернопродуктового подкомплекса

    Get PDF
    Цель. Обосновать ценовую стратегию овладения устойчивым положением предприятий зернопродуктовогоподкомплекса на рынке зерна, муки, круп и хлебобулочных изделий

    Selective C-13-Labels on Repeating Glycan Oligomers to Reveal Protein Binding Epitopes through NMR: Polylactosamine Binding to Galectins

    Get PDF
    A combined chemo-enzymatic synthesis/NMR-based methodology is presented to identify, in unambiguous manner, the distinctive binding epitope within repeating sugar oligomers when binding to protein receptors. The concept is based on the incorporation of C-13-labels at specific monosaccharide units, selected within a repeating glycan oligomeric structure. No new chemical tags are added, and thus the chemical entity remains the same, while the presence of the C-13-labeled monosaccharide breaks the NMR chemical shift degeneracy that occurs in the non-labeled compound and allows the unique identification of the different components of the oligomer. The approach is demonstrated by a proof-of-concept study dealing with the interaction of a polylactosamine hexasaccharide with five different galectins that display distinct preferences for these entities.This research was funded by European Research Council for financial support (ERC-2017-AdG, project number 788143-RECGLYCANMR). We also thank Agencia Estatal de Investigacion (Spain) for project RTI2018-094751-B-C21 and the Severo Ochoa Excellence Accreditation (SEV-2016-0644

    Selective C-13-Labels on Repeating Glycan Oligomers to Reveal Protein Binding Epitopes through NMR: Polylactosamine Binding to Galectins

    Get PDF
    A combined chemo-enzymatic synthesis/NMR-based methodology is presented to identify, in unambiguous manner, the distinctive binding epitope within repeating sugar oligomers when binding to protein receptors. The concept is based on the incorporation of C-13-labels at specific monosaccharide units, selected within a repeating glycan oligomeric structure. No new chemical tags are added, and thus the chemical entity remains the same, while the presence of the C-13-labeled monosaccharide breaks the NMR chemical shift degeneracy that occurs in the non-labeled compound and allows the unique identification of the different components of the oligomer. The approach is demonstrated by a proof-of-concept study dealing with the interaction of a polylactosamine hexasaccharide with five different galectins that display distinct preferences for these entities.This research was funded by European Research Council for financial support (ERC-2017-AdG, project number 788143-RECGLYCANMR). We also thank Agencia Estatal de Investigacion (Spain) for project RTI2018-094751-B-C21 and the Severo Ochoa Excellence Accreditation (SEV-2016-0644

    Zebrafish Peptidoglycan Recognition Proteins Are Bactericidal Amidases Essential for Defense against Bacterial Infections

    Get PDF
    SummaryPeptidoglycan recognition proteins (PGRPs) are structurally conserved through evolution, but their functions in innate immunity are different in invertebrates and vertebrates. We asked what the functions of PGRPs in fish are and whether they are indispensable for defense against infection because fish are the first vertebrates that developed adaptive immunity, but they still rely solely on innate immunity during early development of embryos. We identified and cloned three zebrafish PGRPs and showed that they are highly expressed in eggs, developing embryos, and adult tissues that contact external environment. Zebrafish PGRPs have both peptidoglycan-lytic amidase activity and broad-spectrum bactericidal activity, which is a unique feature. Furthermore, we demonstrated that in the developing zebrafish embryo, one of these PGRPs is essential for defense and survival during bacterial infections. These data demonstrate an absolute requirement for innate immunity in defense against infections in fish embryos and for a PGRP protein for survival in vertebrates
    corecore