Лаборатория углеводов

Руководитель: Бовин Николай Владимирович, д. х. н., профессор
+7 (495) 330-71-38 · professorbovin@yandex.ru

www.carbohydrate.ru/

Синтез олигосахаридов и гликоконъюгатов, супрамолекулярная химия, онкология, группы крови, трансплантология, грипп, естественные антитела, галектины, сиглеки, гликочип, углевод-белковое взаимодействие, гликоландшафт клетки

Лаборатория занимается синтезом олигосахаридов и гликоконъюгатов, а также самоассоциирующих пептидов и гликопептидов, дизайном гликочипа, углевод-белковыми взаимодействиями,  лектинами млекопитающих и бактерий, естественными антителами к углеводам.

Мультиантигенный микрочип

Сотрудники Лаборатории совместно с Consortium for Functional Glycomics разработали гликановый микроэррей (printed glycan array, PGA) – мультиантигенный микрочип, который благодаря наличию в нем опухоле-специфических маркеров (гликанов) дает возможность проведения прогностики, диагностики и мониторинга онкологических заболеваний на новом уровне. Чип используется как в фундаментальных исследованиях, так и при разработке диагностических подходов, с целью диагностики ряда онкологических и репродуктивных заболеваний.

Супрамолекулярная химия

Интерес к самосборке малых молекул  обусловлен возможностью дизайна наноматериалов с индивидуальными свойствами и молекулярных устройств. Для сборки нано-материалов и устройств используются простые молекулы, состоящие почти исключительно из олигоглициновых цепей, когда несколько таких цепей образуют star-like молекулу,  супрамеры собираются благодаря водородным связям. В супрамерах типа (Glycosyl-S)n, S-фрагмент обеспечивает сборку, а углеводная часть обеспечивает биологическую активность и водорастворимость. Подробности здесь.

Синтез олигосахаридов и гликоконъюгатов

Лаборатория занимается синтезом олигосахаридов и гликоконъюгатов – универсальных инструментов для различных биохимических и иммунологических исследований, таких, как изучение специфичности лектинов, разработка ингибиторов адгезии вируса гриппа и др. Подробности здесь и здесь.

Модификация клеточной поверхности

Лаборатория занимается изучением переноса гликолипидов между клетками, а также разработкой синтетических гликолипидов (и аналогично построенных липофильных пептидов), способных  встраиваться практически в любые клетки. Модификация этими молекулами эритроцитов позволяет проводить выявление антител самым простым из возможных методов – агглютинацией. Среди терапевтических подходов в первую очередь необходимо отметить онкотерапию, основанную на инициации иммунного противоопухолевого ответа: инъекция в опухоль гликолипида приводит к немедленной  иммунной атаке предсуществующими естественными антителами, направленными к гликану данного гликолипида (дайте, пожалуйста, ту же ссылку, что в англ. версии).

Выявлен ряд природных антител, которые специфически связываются и разрушают клетки рака молочной железы. Подробности здесь.

Кроме того, Лаборатория занимается разработкой вакцин на основе дендритных клеток.

Лаборатория сотрудничает с подразделениями Института, а также с ФГБУ «Российский онкологический научный центр им. Н. Н. Блохина» Минздрава России,  ФГБУ «Научный центр акушерства, гинекологии и перинатологии имени академика В.И. Кулакова» Минздрава России, Клиника Белвидже каталонского Института здоровья  (Барселона, Испания), Институт исследования здоровья Университета Нанта (Франция), Оклендский технологический университет (Новая Зеландия), Институт Гликомики Университета Гриффита (Австралия), Базельский университет (Швейцария), Масариков университет (Чехия) и рядом других университетов.

Лаборатория (сначала Группа) Углеводов была организована в конце 1988 года, она стала естественным продолжением направления, заложенного в Институте академиком Н.К. Кочетковым, а затем (после его ухода директором в ИОХ) проф. А.Я. Хорлиным («Лаборатория Гликопротеинов и смешанных биополимеров»).

Направления исследований

  • Синтез олигосахаридов и гликоконъюгатов, самоассоциирующих пептидов и гликопептидов;
  • Дизайн диагностического гликочипа;
  • Изучение углевод-белковых взаимодействий;
  • Естественные антитела к углеводам, В1-клеточный иммунитет.
Ф.И.О.ДолжностьЭл. почта
Атанов Владимир Николаевичинженер
Белянчиков Иван Михайловичинж.-иссл.
Вознова Галина Петровнатех.-лаб.
Галанина Оксана Евгеньевна, к. х. н.н.с.
Доброчаева Кира Леонидовнам.н.с.
Корчагина Елена Юрьевна, к. х. н.с.н.с.
Низовцев Алексей Вадимович, к. х. н.инженер
Обухова Полина Сергеевна, к. х. н.н.с.
Овчинникова Татьяна Викторовна, к. х. н.н.с.
Пазынина Галина Валентиновна, к. х. н.с.н.с.
Рапопорт Евгения Марковна, к. х. н.с.н.с.
Рыжов Иван Михайловичн.с.
Саблина Марина Александровна, к. х. н.н.с.
Тузиков Александр Борисович, к. х. н.с.н.с.
Тыртыш Татьяна Викторовна, к. х. н.н.с.
Хасбиуллина Наиля Рамилевнаасп.
Цыганкова Светлана Владимировна, к. х. н.н.с.
Чинарёв Александр Александровичм.н.с.
Шилова Надежда Владимировна, к. х. н.с.н.с.

Избранные публикации

  1. Pazynina G.V., Tsygankova S.V., Sablina M.A., Paramonov A.S., Formanovsky A.A., Bovin N.V. (2016). Synthesis of blood group pentasaccharides ALey, BLey and related tri- and tetrasaccharides. Mendeleev Communications 26, 103–105 ID:1629
  2. Alekseeva A., Kapkaeva M., Shcheglovitova O., Boldyrev I., Pazynina G., Bovin N., Vodovozova E. (2015). Interactions of antitumour Sialyl Lewis X liposomes with vascular endothelial cells. Biochim. Biophys. Acta 1848 (5), 1099–1110 [+]

    Recently, we showed that tetrasaccharide selectin ligand SiaLe(X) provided targeted delivery of liposomes loaded in the bilayer with melphalan lipophilic prodrug to tumour endothelium followed by severe injury of tumour vessels in a Lewis lung carcinoma model. Here, we study the impact of SiaLe(X) ligand on the interactions of liposomes with human umbilical vein endothelial cells (HUVEC) using flow cytometry, spectrofluorimetry and confocal microscopy. Liposomes composed of egg phosphatidylcholine/yeast phosphatidylinositol/1,2-dioleoyl glycerol ester of melphalan, 8:1:1, by mol, and varying percentages of lipophilic SiaLe(X) conjugate were labelled with BODIPY-phosphatidylcholine. The increase in SiaLe(X) content in liposomes led to a proportional increase in their uptake by cytokine-activated cells as opposed to non-activated HUVEC: for 10% SiaLe(X) liposomes, binding avidity and overall accumulation increased 14- and 6-fold, respectively. The early stages of intracellular traffic of targeted liposomes in the activated cells were monitored by co-localisation with the trackers of organelles. Endocytosis of SiaLe(X) liposomes occurred mostly via clathrin-independent pathways, which does not contradict the available literature data on E-selectin localisation in the plasma membrane. Using dual fluorescence labelling, with rhodamine-labelled phospholipid and calcein encapsulated at self-quenching concentrations, we found that SiaLe(X) liposomes undergo rapid (within minutes) internalisation by activated HUVEC accompanied by the disruption of liposomes; non-activated cells consumed a negligible dose of liposomes during at least 1.5h. Our data evidence the selective effect of SiaLe(X) formulations on activated endothelial cells and indicate their potential for intracellular delivery of melphalan lipophilic prodrug.

    ID:1242
  3. Саблина М.А., Тузиков А.Б., Овчинникова Т.В., Михура И.В., Бовин Н.В. (2015). Синтез моно- и ди-О-сульфатов спейсерированной лактозы. Известия Академии наук. Серия Химическая.  (5), 1125–1133 ID:1371
  4. Ryzhov I.M., Korchagina E.Y., Popova I.S., Bovin N.V. (2012). Block synthesis of A tetrasaccharides (types 1, 3, and 4) related to the human ABO blood group system. Carbohydr. Res. 351, 17–25 [+]

    Blood group A tetrasaccharides of different types have the same terminal trisaccharide fragment that allows using a block scheme in their synthesis. 3-Aminopropyl glycosides of tetrasaccharides GalNAcα1-3(Fucα1-2)Galβ1-3GlcNAcβ (A type 1), GalNAcα1-3(Fucα1-2)Galβ1-3GalNAcα (A type 3), and GalNAcα1-3(Fucα1-2)Galβ1-3GalNAcβ (A type 4) were synthesised using acetylated Galα1-3(Fucα1-2)Gal trichloroacetimidate as a glycosyl donor at the key stage.

    ID:1062
  5. Moiseeva E.V., Kuznetsova N.R., Svirshchevskaya E.V., Bovin N.V., Sitnikov N.S., Shavyrin A.S., Beletskaya I.P., Combes S., Fedorov A.Y.u., Vodovozova E.L. (2011). Liposome formulations of combretastatin A4 and its 4-arylcoumarin analogue prodrugs: The antitumor effect in the mouse model of breast cancer. Biochemistry (Moscow) Supplement Series B: Biomedical Chemistry Biochemistry (Moscow) Supplement Series B: Biomedical Chemistry 5 (3), 276–283 [+]

    The antimitotic agent combretastatin A-4 (CA-4) has been recently proposed as an antivascular agent for anticancer therapy. In order to reduce systemic toxicity by means of administration in liposome formulations, new lipophilic prodrugs, oleic derivatives of CA-4 and its 4-arylcoumarin analogue (CA4-Ole and ArC-Ole, respectively), have been synthesized in this study. Liposomes with mean diameter of 100 nm prepared on the basis of egg phosphatidylcholine and baker’s yeast phosphatidylinositol quantitatively included up to 15 mol% of CA4-Ole, or 7 mol% of ArC-Ole. To achieve targeting to neovascular endothelium prodrug bearing liposomes decorated with the tetrasaccharide selectin ligand Sialyl Lewis X (SiaLeX) have been also prepared. The antitumor activity was studied in vivo using the model of slow-growing mouse breast cancer. Under the dose used (22 mg/kg) and the administration protocol (four injections, one per a week, starting from the appearance of palpable tumors) cytostatic CA-4 did not reveal any anticancer effect; moreover, it even stimulated tumor growth. The liposome formulations of CA4-Ole did not demonstrate such stimulation. However, to achieve a pronounced antitumor effect, the number of injections of liposomes should be apparently increased. The cytotoxic activity of a novel antimitotic agent ArC was one order of magnitude lower in the human breast carcinoma cell culture in vitro. Nevertheless, in vivo in the mouse model of breast cancer the antitumor effect of this compound corresponded to the double equivalent dose of CA-4. The results demonstrate perspectives of SiaLeX-liposomes loaded with ArC-Ole: the preparation partially inhibited tumor growth already after the second injection. Thus, subsequent optimization of doses and regimens of administration both for ArC and liposomal ArC-Ole formulations are needed.

    ID:671
  6. Vodovozova E.L., Pazynina G.V., Bovin N.V. (2011). Synthesis of diglyceride conjugate of selectin ligand SiaLeX as a vector for targeting of drug-loaded liposomes. Mendeleev Communications 21 (2), 69–71 [+]

    A conjugate of tetrasaccharide Sialyl Lewis X [SiaLeX, Neu5Acα2-3Galβ1-4(Fucα1-3)GlcNAcβ] 3-aminopropyl glycoside and rac-1,2-dioleoyl-3-carboxymethylene[poly(8–15)oxyethylene]oxyacetylamidopropionylglycerol amenable for the incorporation in lipid bilayer of drug-loaded liposomes to achieve targeting in tumors and inflammation foci was obtained by the formation of carboxamide bond.

    ID:670
  7. Pazynina G., Sablina M., Mayzel M., Nasonov V., Tuzikov A., Bovin N. (2009). Chemical synthesis of 6(GlcNAc)- and 6(Gal)-O-sulfated SiaLe(X) tetrasaccharides in spacer-armed form. Glycobiology 19 (10), 1078–81 [+]

    Practical synthesis of tetrasaccharide sulfates, 6((GlcNAc))-O-Su-SiaLe(X)-OCH(2)CH(2)CH(2)NH(2) and 6((Gal))-O-Su-SiaLe(X)-OCH(2)CH(2)CH(2)NH(2) (Su( )SO(3)H), selectin ligands, and leu- kocyte trafficking agents is presented. Both sulfates were synthesized starting from the same precursor, protected SiaLe(x), by the conventional procedures of carbohydrate chemistry. The sulfated SiaLe(x) derivative was modified at the spacer group to give 6((Gal))-O-Su-SiaLe(x)- OCH(2)CH(2)CH(2)NH-COCH(2)CH(2)C[triple bond]CH, convenient for "click chemistry" mode conjugation with an azido carrier, particularly, for the synthesis of an immunogen.

    ID:236
  8. Huflejt M.E., Vuskovic M., Vasiliu D., Xu H., Obukhova P., Shilova N., Tuzikov A., Galanina O., Arun B., Lu K., Bovin N. (2009). Anti-carbohydrate antibodies of normal sera: findings, surprises and challenges. Mol. Immunol. 46 (15), 3037–49 [+]

    We have used microchip format glycan array to characterize the individual carbohydrate recognition patterns by antibodies (Ab) in sera of 106 healthy donors. The glycan library included blood group antigens and other most frequent terminal oligosaccharides and their cores of mammalian N- and O-linked glycoproteins and glycolipids, tumor-associated carbohydrate antigens, and common components of bacterial/pathogenic polysaccharides and lipopolysaccharides, totally 205 glycans. The serum Ab interacted with at least 50 normal human glyco-motifs. Apart from expected blood group-, xeno- (heterophil) and infection-related binding activities, we observed a number of new and unexpected features. The surprising, relatively high antibody binding was found to the blood group P(1) and P(k) trisaccharides and H(type 2) trisaccharide. Novel and very high binding activities have been observed towards Galbeta1-3GlcNAc (Le(C)) related glycans, especially 3'-O-Su-Le(C), and towards 4'-O-sulfated lactosamine. Relatively high and uniform Ab binding to GalNAcalpha1-3Gal disaccharide demonstrated absence of correlation with fucosylated blood group A GalNAcalpha1-3(Fucalpha1-2)Gal antigen-similarly to well known relationship between Galalpha1-3Gal and true, fucosylated blood group B Galalpha1-3(Fucalpha1-2)Gal antigen. The binding intensity to Galalpha1-3Galbeta1-4GlcNAc xenoantigen was shown to be rather modest. Absence or very low Ab binding was found against oligosialic acid, sialooligosaccharides except SiaT(n), type 2 backbone glycans such as Le(y), and biantennary N-chain as well as its truncated forms, i.e. without terminal Sia, SiaGal, and SiaGalGlcNAc motifs. We have also found that Ab are capable of recognizing the short inner core typical for glycolipids (-Galbeta1-4Glc) and glycoproteins (-GalNAcalpha) as a fragment of bigger glycans.

    ID:235
  9. Bovin N.V., Tuzikov A.B., Chinarev A.A. (2008). Oligoglycines: Materials with unlimited potential for nanotechnologies. Nanotechnologies in Russia 3 (5-6), 48–61 ID:241
  10. (2008). Mammalian galectins: structure, carbohydrate specificity, and functions. Биохимия 73 (4), 483–497 [+]

     

    Галектины – галактозидсвязывающие белки, объединенные в одну группу по гомологии аминокислотной
    последовательности углеводсвязывающего сайта. Обсуждаются литературные данные о строении галекти!
    нов и их углеводной специфичности. Рассмотрена роль галектинов в регулировке клеточной адгезии, им!
    мунном ответе, при воспалительных процессах и онкотрансформации.

    ID:705
  11. Rapoport E.M., André S., Kurmyshkina O.V., Pochechueva T.V., Severov V.V., Pazynina G.V., Gabius H.J., Bovin N.V. (2008). Galectin-loaded cells as a platform for the profiling of lectin specificity by fluorescent neoglycoconjugates: a case study on galectins-1 and -3 and the impact of assay setting. Glycobiology 18 (4), 315–24 [+]

    The involvement of galectins as pleiotropic regulators of cell adhesion and growth in disease progression explains the interest to define their ligand-binding properties. Toward this end, it is desirable to approach in vivo conditions to attain medical relevance. In order to simulate physiological conditions with cell surface glycans as recognition sites and galectins as mediators of intercellular contacts we developed an assay using galectin-loaded Raji cells. The extent of surface binding of fluorescent neoglycoconjugates depended on the lectin presence and the type of lectin, the nature of the probes' carbohydrate headgroup and the density of unsubstituted beta-galactosides on the cell surface. Using the most frequently studied galectins-1 and -3, application of this assay led to rather equal binding levels for linear and branched oligomers of N-acetyllactosamine. A clear preference of galectin-3 for alpha1-3-linked galactosylated lactosamine was noted. In parallel, a panel of 24 neoglycoconjugates was tested as inhibitors of galectin binding from solution to N-glycans of surface-immobilized asialofetuin. These two assays differ in presentation of the galectin and ligand, facilitating identification of assay-dependent properties. Under the condition of the cell assay, selectivity among oligosaccharides for the lectins was higher, and extraordinary affinity of galectin-1 to 3'-O-sulfated probes in a solid-phase assay was lost in the cell assay. Having introduced and validated a cell assay, the comprehensive profiling of ligand binding to cell-surface-presented galectins is made possible.

    ID:237
  12. (2008). Галектины млекопитающих:структура, углеводная специфичность и функции (обзор). Биохимия , [+]

     

    Галектины – галактозидсвязывающие белки, объединенные в одну группу по гомологии аминокислотной
    последовательности углеводсвязывающего сайта. Обсуждаются литературные данные о строении галекти!
    нов и их углеводной специфичности. Рассмотрена роль галектинов в регулировке клеточной адгезии, им!
    мунном ответе, при воспалительных процессах и онкотрансформации.

    ID:706
  13. Gambaryan A.S., Boravleva E.Y., Matrosovich T.Y., Matrosovich M.N., Klenk H.D., Moiseeva E.V., Tuzikov A.B., Chinarev A.A., Pazynina G.V., Bovin N.V. (2005). Polymer-bound 6' sialyl-N-acetyllactosamine protects mice infected by influenza virus. Antiviral Res. 68 (3), 116–23 [+]

    To develop a mouse model for testing receptor attachment inhibitors of human influenza viruses, the human clinical virus isolate in MDCK cells A/NIB/23/89M (H1N1) was adapted to mice by serial passaging through mouse lungs. The adaptation enhanced the viral pathogenicity for mice, but preserved the virus receptor binding phenotype, preferential binding to 2-6-linked sialic acid receptors and low affinity for 2-3-linked receptors. Sequencing of the HA gene of the mouse-adapted virus A/NIB/23/89-MA revealed a loss of the glycosylation sites in positions 94 and 163 of HA1 and substitutions 275Asp-->Gly in HA1 and 145Asn-->Asp in HA2. The four mouse strains tested differed significantly in their sensitivity to A/NIB/23/89-MA with the sensitivity increasing in the order of BALB/cJCitMoise, C57BL/6LacSto, CBA/CaLacSto and A/SnJCitMoise strains. Testing of protective efficacy of the polyacrylamide conjugate bearing Neu5Acalpha2-6Galbeta1-4GlcNAc trisaccharide under conditions of lethal or sublethal virus infection demonstrated a strong protective effect of this preparation. In particular, aerosol treatment of mice with the polymeric attachment inhibitor on 24-110 h after infection completely prevented mortality in sensitive animals and lessened disease symptoms in more resistant mouse strains.

    ID:238
  14. Mochalova L.V., Korchagina E.Y., Kurova V.S., Shtyria J.A., Gambaryan A.S., Bovin N.V. (2005). Fluorescent assay for studying the substrate specificity of neuraminidase. Anal. Biochem. 341 (1), 190–3 [+]

    In this article, we propose a simple and sensitive fluorescent method for determining the neuraminidase specificity using BODIPY-labeled trisaccharides as substrates.

    ID:239
  15. Blixt O., Head S., Mondala T., Scanlan C., Huflejt M.E., Alvarez R., Bryan M.C., Fazio F., Calarese D., Stevens J., Razi N., Stevens D.J., Skehel J.J., van Die I., Burton D.R., Wilson I.A., Cummings R., Bovin N., Wong C.H., Paulson J.C. (2004). Printed covalent glycan array for ligand profiling of diverse glycan binding proteins. Proc. Natl. Acad. Sci. U.S.A. 101 (49), 17033–8 [+]

    Here we describe a glycan microarray constructed by using standard robotic microarray printing technology to couple amine functionalized glycans to an amino-reactive glass slide. The array comprises 200 synthetic and natural glycan sequences representing major glycan structures of glycoproteins and glycolipids. The array has remarkable utility for profiling the specificity of a diverse range of glycan binding proteins, including C-type lectins, siglecs, galectins, anticarbohydrate antibodies, lectins from plants and microbes, and intact viruses.

    ID:38
  16. Шиян С.В., Зуева В.С., Насонов В.В., Жигис Л.С., Цой Н.С., Бовин Н.В. (2004). Сиалирование N-углеводных цепей гликопротеинов с помощью иммобилизованной транс-сиалидазы Trypanosoma cruzi. Биоорг. хим. 30 (4), 1–9 ID:208
  17. Gambaryan A.S., Tuzikov A.B., Pazynina G.V., Webster R.G., Matrosovich M.N., Bovin N.V. (2004). H5N1 chicken influenza viruses display a high binding affinity for Neu5Acalpha2-3Galbeta1-4(6-HSO3)GlcNAc-containing receptors. Virology 326 (2), 310–6 [+]

    To 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 Neu5Acalpha2-3Gal 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 Neu5Acalpha2-3Galbeta1-3GlcNAc, suggesting that these viruses preferentially recognize sialyloligosaccharide receptors with type 1 core (Galbeta1-3GlcNAc). 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 (Galbeta1-4GlcNAcbeta) and bound sulfated trisaccharide Neu5Acalpha2-3Galbeta1-4(6-HSO3)GlcNAcbeta (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.

    ID:37
  18. Bovin N.V., Tuzikov A.B., Chinarev A.A., Gambaryan A.S. (2004). Multimeric glycotherapeutics: new paradigm. Glycoconj. J. 21 (8-9), 471–8 [+]

    The general principle of anti-adhesion therapy is the inhibition of microorganism adhesion to the host cell with the help of a soluble receptor analog. Despite an evident attractiveness of the concept and its long existence, the therapeutics of the 'post-antibiotic era' have not yet appeared. This can be explained by the contradictoriness of requirements for anti-adhesion drugs: to be efficient a drug must be multivalent, i.e. large molecule, but to obtain FDA approval it should be a small molecule. A way to overcome this contradiction is self-assembly of glycopeptides. The carbohydrate part of glycopeptide is responsible for binding with the lectin of microorganisms, whereas a simple peptide part is responsible for an association to the so-called tectomers. Depending on the structure, tectomers are formed either spontaneously or upon promotion of a microorganism. In particular, sialopeptide, which is capable of converting to a tectomer only in the presence of the influenza virus, has been obtained. Thus, the new strategy of anti-adhesion therapy can be formulated as follows: (1) identification of oligosaccharide-receptor for a particular virus (bacteria); (2) optimization of the peptide part; (3) conventional trials. The expected advantages of this strategy are the following: (i) no polymer; (ii) a virion completely covered with a tectomer, i.e. blocking is both complete and irreversible; (iii) rapid and rational lead identification and optimization; (iv) minimum side effects; (v) potential for microorganism resistance to natural receptor is lower than in the case of mimetics.

    ID:240
  19. Tuzikov A.B., Chinarev A.A., Gambaryan A.S., Oleinikov V.A., Klinov D.V., Matsko N.B., Kadykov V.A., Ermishov M.A., Demin I.V., Demin V.V., Rye P.D., Bovin N.V. (2003). Polyglycine II nanosheets: supramolecular antivirals? Chembiochem 4 (2-3), 147–54 [+]

    Tetraantennary peptides [glycine(n)-NHCH(2)](4)C can form stable noncovalent structures by self-assembly through intermolecular hydrogen bonding. The oligopeptide chains assemble as polyglycine II to yield submicron-sized, flat, one-molecule-thick sheets. Attachment of alpha-N-acetylneuraminic acid (Neu5Acalpha) to the terminal glycine residues gives rise to water-soluble assembled glycopeptides that are able to bind influenza virus multivalently and inhibit adhesion of the virus to cells 10(3)-fold more effectively than a monomeric glycoside of Neu5Acalpha. Another antiviral strategy based on virus-promoted assembly of the glycopeptides was also demonstrated. Consequently, the self-assembly principle offers new perspectives on the design of multivalent antivirals.

    ID:36
  20. Рапопорт Е.М., Некрасов М.В., Хайдуков С.В., Свирщевская Е.В., Жигис Л.С., Козлов Л.В., Баталова Т.Н., Зубов В.П., Бовин Н.В. (2000). Изучение клеточной локализации галактозосвязывающего лектина из сыворотки крови человека. Биохимия 65 (11), 1558–1563 ID:207
  21. Mikhalchik E.V., Shiyan S.D., Bovin N.V. (2000). Carbohydrate-carbohydrate interaction: zymosan and beta-glucan from Saccharomyces cerevisiae bind mannosylated glycoconjugates. Biochemistry Mosc. 65 (4), 494–501 [+]

    Zymosan from cell wall of the yeast Saccharomyces cerevisiae was found to interact with synthetic and natural glycoconjugates; mannose-rich glycoprotein N-chains demonstrated the maximal affinity. The carbohydrate-carbohydrate nature of the interaction has been confirmed by the following data: 1) periodate treatment of the zymosan impairs the binding; 2) neither protease nor alkali treatment of the zymosan weaken the binding; 3) beta-glucan from S. cerevisiae, which is the major zymosan component, interacts with glycoconjugates similarly to zymosan. The binding is reversible, Ca2+-dependent, and cooperative; it can be dose-dependently inhibited by saccharides relative to one of the partners of the carbohydrate-carbohydrate interaction.

    ID:35
  22. Bovin N.V., Korchagina E.Y., Zemlyanukhina T.V., Byramova N.E., Galanina O.E., Zemlyakov A.E., Ivanov A.E., Zubov V.P., Mochalova L.V. (1993). Synthesis of polymeric neoglycoconjugates based on N-substituted polyacrylamides. Glycoconj. J. 10 (2), 142–51 [+]

    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.

    ID:34

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Бовин Николай Владимирович

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