Bi-substrate inhobitors of human pyrimidine 5’-nucleosidases

0429301 - ÚOCHB 2015 CZ eng C - Konferenční příspěvek (zahraniční konf.)
Šimák, Ondřej - Pachl, Petr - Jandušík, T. - Brynda, Jiří - Buděšínský, Miloš - Rosenberg, Ivan
Bi-substrate inhobitors of human pyrimidine 5’-nucleosidases.
Chemistry of Nucleic Acid Components. 16th Symposium. Praha: Institute of Organic Chemistry and Biochemistry AS CR, v. v. i, 2014 - (Hocek, M.), s. 381-382. Collection Symposium Series, 14. ISBN 978-80-86241-50-0.
[Symposium on Chemistry of Nucleic Acid Components /16./. Český Krumlov (CZ), 08.06.2014-13.06.2014]
Grant CEP: GA ČR GA13-26526S; GA ČR GA13-24880S; GA TA ČR TA03010719
Institucionální podpora: RVO:61388963 ; RVO:68378050
Klíčová slova: 5’-nucleosidases * NPAs * bi-substrate inhibitors
Kód oboru RIV: CC - Organická chemie

The work is aimed at the synthesis of bi-substrate inhibitors of 5’-nucleosidases. The pyrimidine nucleobase of lead compound was derivatized in the 5-position with various phosphonic acids differing in conformational flexibility and in the length of alkyl side chain carrying phosphonate group. The phosphonic acid with optimal linker can reach the phosphate binding side and make strong interaction with the enzyme. Inhibition activity of such inhibitors and crystal structure of inhibitor-enzyme complex will be presented.
Trvalý link: http://hdl.handle.net/11104/0234531