Бовин Николай Владимирович

Личная информация

Работа по профессии

1976-1985: сотрудник ИБХ им. М.М. Шемякина АН СССР;

1985-1988: руководитель подразделения во Всесоюзном Институте биотехнологии Министерства медицинской промышленности СССР;

1988-наст.вр.: руководитель группы, ныне лаборатории Углеводов Учреждения Российской академии наук Института биоорганической химии им. академиков М.М. Шемякина и Ю.А. Овчинникова РАН

 

Преподавательская деятельность

 

Курс "Гликобиология" для студентов 4 курса биологического факультета МГУ и факультета молекулярной и биологической физики МФТИ (на базе Учебно-научного центра ИБХ РАН).

Образование

Период обученияСтрана, городУчебное заведениеДополнительная информация
1971–1976 Россия, Москва Московский государственный университет имени М.В. Ломоносова (МГУ), химический факультет Диплом химика
1982 Россия, Москва Институт биоорганической химии имени М.М. Шемякина АН СССР (ИБХ) Присуждена учёная степень кандидата химических наук за диссертацию «Синтез группоспецифических олигосахаридов крови H, A и Lea, и их иммобилизация на полимерной матрице»
1993 Россия, Москва Институт биоорганической химии им. академиков М.М. Шемякина и Ю.А. Овчинникова РАН (ИБХ) Присуждена учёная степень доктора химических наук за диссертацию «Неогликоконъюгаты: синтез и применение для гемо- и онкодиагностики»
2001 Россия, Москва Институт биоорганической химии им. академиков М.М. Шемякина и Ю.А. Овчинникова РАН (ИБХ) Присвоено учёное звание профессора

Основные научные результаты

Химический синтез. Синтезировано более 200 наиболее биологически значимых олигосахаридов – терминальных фрагментов и коровых участков углеводных цепей гликопротеинов и гликолипидов человека, в том числе опухоле-ассоциированных и трансплантационных антигенов; лигандов селектинов, сиглеков и галектинов.

Разработан универсальный подход к синтезу неогликоконъюгатов – инструментов исследования углевод-связывающих белков поверхности клеток; эти гликоконъюгаты позволяют нам проводить в течение многих лет собственные гликобиологические исследования, а также совместные работы с партнерами в других странах.

Супрамолекулярная химия. На основе структуры полиглицин II cконструированы пептиды и гликопептиды, способные к самоассоциации в воде, движущей силой ассоциации являются исключительно водородные связи, ассоциаты представляют собой плоские двумерные кристаллы. Обнаружено явление кооперативности при термической олигомеризации глицинамида в пребиотических условиях.

Вирусология. Изучена рецепторная специфичность различных штаммов вирусов гриппа А и В; показано, что все клинические и неадаптированные лабораторные штаммы (в отличие от лабораторных, и в отличие от общепринятого мнения) связываются с одним и тем же рецептором, а именно 6’SLN. Найден рецептор птичьих вирусов H5N1, представляющий собой сульфатированный олигосахарид 6-O-Su-3’SLN; вирусы, выделенные от заболевших людей, сохраняют эту специфичность. Предложен новый принцип противовирусной терапии, опирающийся на само-ассоциирующие гликопептиды.

Гликобиология. Идентифицирован новый фермент, вызывающий атеросклеротические изменения – человеческая транс-сиалидаза; показано, что фермент имеет широкую углеводную специфичность, способен как сиалилировать, так и десиалилировать липопротеины низкой плотности. Найдено, что Р-селектин способен связываться с незаряженными лигандами, и в то же время с заряженными неуглевдными лигандами.

Выявлено участие олигосахарида Galb1-3GalNAcb1-4Galb1-4Glc в фагоцитозе апоптозных клеток. Найдено, что лигандом NK-специфичного сиглека-7 является олигосиаловый фрагмент ганглиозидов и гликопротеинов, сиглека-8  – олигосахарид 6’-O-Su-3’SLN,  а сиглека-9 – олигосахарид 6-O-Su-SiaLeX. Обнаружено, что специфичность клеточных галектинов регулируется цис-взаимодействием с соседними гликоконъюгатами. Разработан метод изучения олигосахаридной специфичности нейраминидаз. Разработан углеводный микрочип, с его помощью в крови человека обнаружены маскированные ауто-антитела к ряду углеводных антигенов.

Объяснена природа человеческих группоспецифических антител так называемой АВ-специфичности. Разработан метод мягкой модификации живых клеток олигосахаридами.

Членство в научных обществах

  • Член Учёного и Диссертационного советов ИБХ им. М.М. Шемякина и Ю.А. Овчинникова РАН;
  • Член Учёного совета ИОХ им. Н.Д. Зелинского РАН;
  • Член редколлегии журналов  Glycoconjugate Journal и Carbohydrate Letters;
  • Национальный представитель в IGO (International Glycocojugate Organization).

Избранные публикации

  1. 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
  2. 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
  3. Kuznetsova N.R., Stepanova E.V., Peretolchina N.M., Khochenkov D.A., Boldyrev I.A., Bovin N.V., Vodovozova E.L. (2014). Targeting liposomes loaded with melphalan prodrug to tumour vasculature via the Sialyl Lewis X selectin ligand. J Drug Target 22 (3), 242–250 [+]

    Earlier we showed that liposome formulation of DL-melphalan lipophilic prodrug bearing tetrasaccharide Sialyl Lewis X (SiaLe(X)) caused prolonged therapeutic effect on mammary cancer in mice. Here, we compare antivascular effect of SiaLe(X)-liposomes loaded with diglyceride ester of melphalan (Mlph) against SiaLe(X)-free formulation in Lewis lung carcinoma model. Methods: Liposomes of egg phosphatidylcholine/yeast phosphatidylinositol/1,2-dioleoyl glycerol (DOG) conjugate of Mlph/±SiaLe(X)-PEG8-15-DOG, 8:1:1:0.2 by mol, were prepared by standard extrusion. After two intravenous injections with Mlph or liposomes under either standard or delayed treatment protocols, vascular-disrupting effects of the preparations were evaluated basing on tumour section histomorphology, lectin perfusion assay and immunohistochemistry (anti-CD31 staining) data. Also, untreated mice were administered with fluorescently-labelled liposomes to assess their distribution in tumour sections with confocal laser scanning microscopy. Results: Two injections of SiaLe(X)-liposomes reproducibly caused severe injuries of tumour vessels. SiaLe(X)-liposomes co-localized with CD31 marker on vascular endothelium while the non-targeted formulation extravasated into tumour. Discussion: Cytotoxic SiaLe(X)-liposomes exhibit superior vascular-disrupting properties compared to non-targeted liposomes, yet the effect starts to transform into gain in tumour growth inhibition only under delayed treatment regimen. Conclusion: SiaLe(X)-ligand provides targeting of cytotoxic liposomes to tumour endothelium and subsequent antivascular effect.

    ID:997
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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
  11. 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
  12. 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
  13. 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
  14. 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
  15. 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
  16. 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
  17. 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
  18. Vodovozova E.L., Moiseeva E.V., Grechko G.K., Gayenko G.P., Nifant'ev N.E., Bovin N.V., Molotkovsky J.G. (2000). Antitumour activity of cytotoxic liposomes equipped with selectin ligand SiaLe(X), in a mouse mammary adenocarcinoma model. Eur. J. Cancer 36 (7), 942–9 [+]

    The overexpression of lectins by malignant cells compared with normal ones can be used for the targeting of drug-loaded liposomes to tumours with the help of specific carbohydrate ligands (vectors). Recently we have shown that liposomes bearing specific lipid-anchored glycoconjugates on a polymeric matrix bind in vitro to human malignant cells more effectively and, being loaded with a lipophilic prodrug of merphalan, reveal higher cytotoxic activity compared with unvectored liposomes. In this study, carbohydrate-equipped cytotoxic liposomes were tested in vivo in a mouse breast cancer model, BLRB-Rb (8.17)1Iem strain with a high incidence of spontaneous mammary adenocarcinoma (SMA). Firstly, a cell line of the SMA was established which was then used to determine the specificity of the tumour cell lectins. After screening of the lectin specificity of a number of fluorescent carbohydrate probes, SiaLe(X) was shown to be the ligand with the most affinity, and a lipophilic vector bearing this saccharide was synthesised. Then different liposomal formulations of the synthetic merphalan lipid derivative and SiaLe(X) vector were prepared and applied in the treatment of mice with grafted adenocarcinomas. The results of the tumorigenesis data show that the therapeutic efficacy of merphalan increases sharply after its insertion as a lipophilic prodrug into the membrane of SiaLe(X)-vectored liposomes.

    ID:109
  19. 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
  20. Mikhura I.V., Formanovsky A.A., Bovin N.V. (1999). One-pot scale synthesis of trifluoroacetamidopropyl 2-O-acetyl-4,6-O-benzylidene-beta-D-galactopyranoside. Carb. lett. 3 (5), 305–308 [+]

    В публикации показано, что в зависимости от выбранной схемы и реагентов можно избирательно защищать гидроксильные группы во 2-ом либо 3-ем месте спейсерированного 4,6-О-бензилиден-β-D-галактопиранозида. Во втором случае три стадии реакции проводятся без выделения.

    ID:44
  21. Vodovozova E.L., Gayenko G.P., Razinkov V.I., Korchagina E.Y., Bovin N.V., Molotkovsky J.G. (1998). Saccharide-assisted delivery of cytotoxic liposomes to human malignant cells. Biochem. Mol. Biol. Int. 44 (3), 543–53 [+]

    The overexpression of lectins by malignant cells was applied for in vitro targeting of liposomes equipped with a saccharide vector and loaded in the lipid phase with a lipid derivative of anticancer agent sarcolysine. The lectin specificity of human leukemia HL-60 and human lung adenocarcinoma ACL cells was revealed by tests with fluorescein-labeled sugar probes. With the help of fluorescent lipid dye it was shown that active saccharide ligands increased the level of the vectored liposome binding to malignant cells by 50-80% as compared to liposomes without vector or with inactive one. The degree of liposome/cell membrane fusion was monitored fluorometrically and was shown to be complete and independent of the vectors. The targeted drug-loaded liposomes had the cytotoxic activity 2-4 times higher as compared to the vector-free ones.

    ID:110
  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