Isolierung, Struktur und Inhibierung von Nematoden-Chitinase
Zusammenfassung der Projektergebnisse
In der Arbeitsgruppe Peter wurden Pseudo-Di- und Tri-saccharide synthetisiert, in denen zwei GlcNAc-Reste S-glycosidisch verknüpft sind. Als Aglycone dienten u. a. aromatische bzw. heteroaromatische Reste. Ferner wurden Thioacetamide und Thiazoline von Chito- bzw. Thiochitooligomeren hergestellt. Enzymatische Untersuchungen mit Chitinasen verschiedener Herkunft zeigten bei den Disacchariden eine noch nicht optimale Inhibitorwirkung. Weiterhin haben wir alle sechs isomere Tetrasaccharide der Zusammensetzung β-1,4-(GlcNAc)2(GlcN)2 synthetisiert. Diese Arbeiten wurden erst kürzlich abgeschlossen, so dass Daten zur biologischen Aktivität noch nicht vorliegen. In the project work of the Lucius group, a soluble enzymatically active nematode chitinase was produced that can be used in the characterisation of potential inhibitors, and we have shown at the molecular level that chitinases are important in the development of filarial parasites and are thus good targets for drug and immune intervention. Further attempts to characterize the structure after crystallization of various forms of recombinant chitinase are now undertaken in cooperation with the group of Wolfgang Höhne (Charité Berlin). This group is also in the process to develop peptide inhibitors of A. viteae chitinase that we are currently testing for biological activity on microfilariae and adult A. viteae.
Projektbezogene Publikationen (Auswahl)
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„Molecular characterization of Acanthocheilonema viteae chitinase”. Meeting of the Federation of African Societies for Biochemistry and Molecular Biology, Yaounde, Cameroon, 2003
Tachu, B.J., Lucius, R., Hirzmann, J., Titanji, V.P.K., Pogonka T.
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„Molecular characterization of Acanthocheilonema viteae chitinase genes”. 21st Meeting of the German Society for Parasitology, Würzburg, Germany, 2004
Tachu, B.J., Lucius, R., Hirzmann, J., Titanji, V.P.K., Pogonka T.
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„Studies on subunit vaccines against infection with the parasitic nematode Acathocheilonema viteae in a rodent model”. Vaccine Congress, Berlin, Germany, 2005
Sereda, M.J., Pillai, S., Tachu, B.J., Hartmann, S., Pogonka, T., Lucius, R.
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(2006) Synthesis and crystal structure of p-methoxyphenyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranoside. Anal. Sci. X-ray Struc. Anal. Online 22, x113-x114
Peikow, D., Geßner, A., Matern, C.-M., Peter, M. G., Kelling, A., Schilde, U.
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Molecular and immunological characterisation of Acanthocheilonema viteae chitinase. Dissertation, Humboldt University Berlin, 2006
Babila Julius Tachu
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Synthese und Glycosidashemmung von Thio-analogen Kohlenhydraten. Dissertation, Universität Potsdam. (2006)
Dirk Peikow
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“Synthesis of Partially Acetylated Chitotetraoses”. 10th ICCC-Euchis’ 06, Montpellier, France, 6-9 September, 2006
Issaree, A.; Peter, M. G.
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„Synthesis of thiooligosaccharides and glycosides”. 10th ICCC-Euchis’06, Montpellier, France, 6-9 September, 2006
Peikow, D., Matern, C.-M., Spindler, K.-D., Schilde, U., Peter, M. G.
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„Synthesis of thiooligosaccharides and glycosides”. Tag der Chemie, Berlin, 28. Juni 2006
Peikow, D., Matern, C.-M., Spindler, K.-D., Schilde, U., Peter, M. G.
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Developmental and functional characterization of cystatin and chitinase of Acanthocheilonema viteae. Dissertation, Humboldt-Universität zu Berlin, Mai 2007
Smitha Pilla
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“Synthesis of Partially Acetylated Chitotetraoses”. 8th Tetrahedron Symposium: Challenges in Organic Chemistry, Berlin, 26-29 June, 2007
Issaree, A., Peter, M. G.
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Essential role of chitinase in the life cycle of the filarial nematode Acanthocheilonema viteae. Infection and Immunity, 2008, 221-228
Babila Julius Tachu, Richard Lucius, Smitha Pillai, and Thomas Pogonka
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Synthesis of the six isomers of β-1,4-linked tetrasaccharides composed of two glucosamine and two N-acetylglucosamine residues. International Symposium on Natural Products, Kasane, Botswana, 24. – 29.02.2008
Issaree, A., Vijayakrishnan, B., Peter, M.G.
