Ass.Professor Dr. Alla Zamyatina
Alla Zamyatina

University of Natural Resources and Life Sciences
Department of Chemistry
Muthgasse 18, 1190 Vienna, Austria

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Major Research Interests

  • The main topic of our research is to comprehend the structural and molecular basis of recognition of Lipopolysaccharide, a Pathogen - associated Molecular Pattern of Gram-negative bacteria, by its mammalian Pattern Recognition Receptor, Toll-like Receptor 4. Lipopolysaccharide (LPS) counts to the foremost virulence factors of Gram-negative infection. A glycophospholipid Lipid A, an endotoxic portion of LPS, initiates activation of the innate immune system by binding to the Toll-like Receptor 4 (TLR4) – myeloid differentiation 2 (MD-2) complex. The central point of investigations focusses on elucidation of structure-activity relationships within homodimeric Lipid A/MD-2/TLR4 receptor complex.

  • Chemical synthesis and exploration of the immuno-biological properties of diverse Lipid A variants corresponding to complex naturally occurring bacterial LPS as well as specifically designed Lipid A mimetics.

  • Development of agonistic and antagonistic TLR4 ligands as potential immuno-modulating therapeutics and anti-sepsis drug candidates.
  • Syntetic Endotoxin Mimetics (Read more...)

    • Selected contributions:
    • Artner, D., Oblak, A., Ittig, S., Garate, J.A., Horvat, S., Arrieumerlou, C., Hofinger, A., Oostenbrink, C., Jerala, R., Kosma, P., and Zamyatina, A. (2013) Conformationally constrained Lipid A mimetics for exploration of structural basis of TLR4/MD-2 activation by lipopolysaccharide. ACS Chem.Biol. 8, 2423-2432.

    • Adanitsch, F., Ittig, S., Stöckl, J., Oblak, A., Haegman, M., Jerala, R., Beyaert, R., Kosma, P., and Zamyatina, A. (2014) Development of αGlcN(1↔1)αMan-Based Lipid A Mimetics as a Novel Class of Potent Toll-like Receptor 4 Agonists. J.Med.Chem. 57, 8056-8071.

    • Baum, D., Kosma, P., and Zamyatina, A. (2014) Synthesis of zwitterionic 1,1-α,α-glycosylphosphodiester: a partial structure of galactosamine-modified Francisella Lipid A. Org.Lett. 16, 3772-3775.

    • Hollaus, R.; Ittig, S.; Hofinger, A.; Haegman, M.; Beyaert, R.; Kosma, K.; Zamyatina, A. Chemical synthesis of Burkholderia Lipid A modified with glycosyl phosphodiester-linked 4-amino-4-deoxy-β-L-arabinose and its immunomodulatory potential. (2015), Chem. Eur. J. 21, 4102-4114

    • Garate, J. A.; Stöckl, J.; del Carmen Fernández-Alonso, M.; Artner, D.; Haegman, M.; Oostenbrink, C.; Jiménez-Barbero, J.; Beyaert, R.; Heine, H.; Kosma, P.; Zamyatina, A. Anti-endotoxic activity and structural basis for human MD-2•TLR4 antagonism of tetraacylated lipid A mimetics based on βGlcN(1↔1)αGlcN scaffold. (2015), Innate Immun. 21, 490-503

  • The synthesis of heptose-containing partial structures of the Core-region of LPS and their biosynthetic precursors allows for exploration of the LPS biosynthetic pathways.

    • Selected contributions:
    • Zamyatina, A.; Gronow, S.; Oertelt, C.; Puchberger, M.; Brade, H. and Kosma, P. (2000) Efficient chemical synthesis of the two anomers of ADP-L-glycero- and D-glycero-D-manno-heptopyranose allows the determination of the substrate specificities of bacterial heptosyltransferases. Angew. Chemie. Int. Ed. 39, 4150-4153.

    • Kneidinger, B.; Marolda, C.; Graninger, M.; Zamyatina, A.; McArthur, F.; Kosma, P.; Valvano, M.A. and Messner, P. (2002) Biosynthesis pathway of ADP-L-glycero-β-D-manno-heptose in Escherichia coli. J. Bacteriol. 184, 363-369.

    • Lu, Q.; Yao, Q.; Xu, Y.; Li, L.; Li, S.; Liu, Y.; Gao, W.; Niu, M.; Sharon, M.; Ben-Nissan, G.; Zamyatina, A.; Liu, X.; Chen, S. and Shao, F. (2014) An Iron-Containing Dodecameric Heptosyltransferase Family Modifies Bacterial Autotransporters in Pathogenesis. Cell Host & Microbe 16, 351-363