Název: Modulation of human telomerase activity by nucleoside and nucleotide analogues
Překlad názvu: Modulation of human telomerase activity by nucleoside and nucleotide analogues
Autoři: Hájek, Miroslav ; Votruba, Ivan (vedoucí práce) ; Fajkus, Jiří (oponent) ; Hejnar, Jiří (oponent)
Typ dokumentu: Disertační práce
Rok: 2008
Jazyk: eng
Abstrakt: CONCLUSIONS Considering human telomerase as a promising target of anti-cancer therapy, the thesis deals with the study of inhibitory potency of selected ANP diphosphates towards telomerase, and the capability of nucleoside-type DNA methylation inhibitors to inhibit hTERT expression, knowing that hTERT expression closely correlates with telomerase activity in vitro and in vivo. The results can be summarized as follows: All the purine ANP diphosphates except for (S)-PMPApp and 6-Me2PMEDAPpp show dose- dependent inhibition of human telomerase in cell-free assay, the adenine derivatives are less effective inhibitors than the guanine derivatives. The only two pyrimidine ANP diphosphates tested (PMECpp and PMETpp) do not show any significant inhibitory potency towards telomerase. Activity of tested ANPs on telomerase is limited to their diphosphates (ANPpp) only. (R)-enantiomers are more inhibitory compared to (S)-enantiomers. This indicates that absolute configuration plays an important role in the telomerase inhibition and that the enzyme distinguishes between the (R)- and (S)-enantiomers. PMEGpp is the most potent human telomerase inhibitor among all ANPs studied with the IC50 value of 12.7 ± 0.5 mol.l-1 at 125 M dNTPs. Its inhibitory potency towards telomerase is comparable to that of ddGTP (IC50...

Instituce: Fakulty UK (VŠKP) (web)
Informace o dostupnosti dokumentu: Dostupné v digitálním repozitáři UK.
Původní záznam: http://hdl.handle.net/20.500.11956/92467

Trvalý odkaz NUŠL: http://www.nusl.cz/ntk/nusl-368977


Záznam je zařazen do těchto sbírek:
Školství > Veřejné vysoké školy > Univerzita Karlova > Fakulty UK (VŠKP)
Vysokoškolské kvalifikační práce > Disertační práce