Staff Joanna CIEŚLA, Magdalena DĄBROWSKA, Jolanta M. DZIK, Tomasz FRĄCZYK, Adam JARMUŁA, Anna
DOWIERCIAŁ, Zbigniew ZIELIŃSKI
Different aspects of thymidylate biosynthesis, such as its
enzymology, regulation and inhibition, are investigated.
Problems connected with thymidylate synthase being a target
in chemotherapy, including search for new drugs, drug
resistance, specificity and mechanism of action, as well as
mechanisms of enzyme inhibition and its specificity, are of
particular interest. Developmental regulation of enzymes
involved in thymidylate biosynthesis in nematodes is studied
as a potential new chemotherapy target. Certain molecular
aspects of host immunological response to Trichinella
spiralis infection are also studied.
Current research activities
search for new thymidylate synthase inhibitors;
studies on RNA binding by thymidylate synthase;
studies on inhibition by thymidylate synthase protein of its own mRNA translation;
studies of a potential new target of antiparasitic chemotherapy; developmental pattern of expression of enzymes involved in thymidylate biosynthesis in Trichinella spiralis, T. pseudospiralis and Caenorhabditis elegans, reflecting certain uniqueness of nematode cell cycle regulation, is investigated;
studies aimed at testing of the potential of post-translational modifications to influence such thymidylate synthase properties as sensitivity to inhibition, catalytic efficiency, and certain functional properties: potential to bind its own mRNA and repress its own mRNA translation;
studies of the mechanism of thymidylate synthase reaction and its inhibition by the molecular modeling (molecular dynamics, quantum mechanics) and crystallography;
studies of the molecular mechanisms of immunological response to parasitic antigens in lungs.
Jarmuła A, Dowierciał A, Rode W (2008) A molecular modeling study of the interaction of 2’-fluoro-substituted analogues of dUMP/FdUMP with thymidylate synthase. Bioorg. Med. Chem. Letters, w druku
Cieśla J, Jagielska E, Dąbrowska M, Maley F, Rode W (2007) Binding and repression of translation of the cognate mRNAs by rat and Trichinella spiralis thymidylate synthases, apparently disconnected phenomena, are not prevented by dUMP, N5,10-methylenetetrahydrofolate or 5-fluoro-dUMP. W Proceedings of the 13th International Symposium on Chemistry & Biology of Pteridines & Folates, Red Jansen G., Peters G.J., SPS Verlagsgesellschaft mbH, Heilbronn, str 91-104..
Ziemkowski P, Felczak K, Poznański J, Kulikowski T, Zieliński Z, Cieśla J, Rode W (2007) Interactions of 2’-fluoro-substituted dUMP analogues with thymidylate synthase. Biochem. Biophys. Res. Commun. 362:37-43.
Jarmuła A, Cieplak P, Krygowski TM, Rode W (2007) The effect of 5-substitution in the pyrimidine ring of dump on the interaction with thymidylate synthase: Molecular modeling and QSAR. Bioorg. Med. Chem. 15: 2346-2358.
Dąbrowska M, Hendrikx J, Skierski J, Malinowska M, Bertino JR, Rode W (2007) EGFP fluorescence as an indicator of cancer cells response to methotrexate. Eur. J. Pharmacol. 555: 93-99.