19916-78-0Relevant articles and documents
Direct effect of heavy ions and electrons on 2′-deoxyguanosine in the solid state
Gromova, Marina,Nardin, Robert,Cadet, Jean
, p. 1365 - 1374 (1998)
Attempts have been made in this work to gain insights into the mechanisms of the formation of degradation products arising from the exposure of 2′-deoxyguanosine (dGuo) in the solid state to O7+ heavy ions of 10.6 MeV u-1 (LET ≈ 500 keV μm-1). The main decomposition products of dGuo have been isolated by reversed-phase high performance liquid chromatography and characterized by extensive spectroscopic (1H and 13C NMR, mass spectrometry, UV) measurements. Reaction mechanisms, involving the transient formation of sugar and purine radical, are proposed to explain the generation of the heavy ion-mediated degradation products. Another major objective of the present work is the comparison of heavy ion-induced modifications of 2′-deoxyguanosine with those produced by lower LET radiation. For this purpose, the samples of 2′-deoxyguanosine were exposed in the solid state to electrons of 2 MeV (LET ≈ 0.18 keV μm-1). It may be inferred from the results of the qualitative and semi-quantitative comparison that the modifications of the sugar moiety are more efficiently induced by heavy ions than by electrons.
L-thymidine is phosphorylated by herpes simplex virus type 1 thymidine kinase and inhibits viral growth
Spadari,Maga,Focher,Ciarrocchi,Manservigi,Arcamone,Capobianco,Carcuro,Colonna,Iotti,Garbesi
, p. 4214 - 4220 (2007/10/02)
We have demonstrated that herpes simplex 1 (HSV1) thymidine kinase (TK) shows no stereospecificity for D- and L-β-nucleosides. In vitro, L enantiomers are not recognized by human TK, but function as specific substrates for the viral enzyme in the order: L-thymidine (L-T) >> 2'-deoxy- L-guanosine (L-dG) > 2'-deoxy-L-uridine (L-dU) > 2'-deoxy-L-cytidine (L-dC) > 2'-deoxy-L-adenosine (L-dA). HSV1 TK phosphorylates both thymidine enantiomers to their corresponding monophosphates with identical efficiency and the K(i) of L-T (2 μM) is almost identical to the K(m) for the natural substrate D-T (2.8 μM). The L enantiomer reduces the incorporation of exogenous [3H]T into cellular DNA in HeLa TK-/HSV1 TK+ but not in wild-type HeLa cells, without affecting RNA, protein synthesis, cell growth, and viability. L-T markedly reduces HSV1 multiplication in HeLa cells. Our observations could lead to the development of a novel class of antiviral drugs characterized by low toxicity.
