18 research outputs found
HF-EPR, Raman, UV/VIS Light Spectroscopic, and DFT Studies of the Ribonucleotide Reductase R2 Tyrosyl Radical from Epstein-Barr Virus
Epstein-Barr virus (EBV) belongs to the gamma subfamily of herpes viruses, among the most common pathogenic viruses in humans worldwide. The viral ribonucleotide reductase small subunit (RNR R2) is involved in the biosynthesis of nucleotides, the DNA precursors necessary for viral replication, and is an important drug target for EBV. RNR R2 generates a stable tyrosyl radical required for enzymatic turnover. Here, the electronic and magnetic properties of the tyrosyl radical in EBV R2 have been determined by X-band and high-field/high-frequency electron paramagnetic resonance (EPR) spectroscopy recorded at cryogenic temperatures. The radical exhibits an unusually low g1-tensor component at 2.0080, indicative of a positive charge in the vicinity of the radical. Consistent with these EPR results a relatively high C-O stretching frequency associated with the phenoxyl radical (at 1508 cmâ1) is observed with resonance Raman spectroscopy. In contrast to mouse R2, EBV R2 does not show a deuterium shift in the resonance Raman spectra. Thus, the presence of a water molecule as a hydrogen bond donor moiety could not be identified unequivocally. Theoretical simulations showed that a water molecule placed at a distance of 2.6 Ă
from the tyrosyl-oxygen does not result in a detectable deuterium shift in the calculated Raman spectra. UV/VIS light spectroscopic studies with metal chelators and tyrosyl radical scavengers are consistent with a more accessible dimetal binding/radical site and a lower affinity for Fe2+ in EBV R2 than in Escherichia coli R2. Comparison with previous studies of RNR R2s from mouse, bacteria, and herpes viruses, demonstrates that finely tuned electronic properties of the radical exist within the same RNR R2 Ia class
Coricladus quiteriensis gen. et sp. nov., a new conifer in Southern-Brazil Gondwana (Lower Permian, ParanĂĄ Basin)
Curcumin induces senescence of primary human cells building the vasculature in a DNA damage and ATM-independent manner
Sex Differences in Spiritual Coping, Forgiveness, and Gratitude Before and After a Basic Alcohol Addiction Treatment Program
Metabolic N1-Oxidation of 9-Benzyladenine and Isomeric 9-(Nitrobenzyl)Adenines by Hamster Hepatic Microsomes
Adenosine-Derived 5âČ-α-Halo Thioether, Sulfoxide, Sulfone, and (5âČ-Halo)Methylene Analogues. Inhibition of S-Adenosyl-L-Homocysteine Hydrolase
2âČ-Deoxy-2âČ-azidonucleoside analogs: synthesis and evaluation of antitumor and antimicrobial activity
A series of ten pyrimidine nucleosides modified in 2âČ position with azide or amine group was tested for the antibacterial, antifungal and cytotoxic activity. The cytotoxic effect was determined on three cancer (CCRF-CEM, MCF7, HeLa) and one normal (HEK293) cell lines, while antibacterial activity was evaluated on five bacterial strains. Among others, 2âČ-azido-2âČdeoxycytidine and 2âČ-amino-2âČ-deoxycytidine exhibited the strongest antiproliferative activity at 200 ÎŒM concentration, decreasing the viability of CCRF-CEM cells to 33 ± 1 and 36 ± 2%, respectively. Newly synthesized 2âČ-amino-2âČ-deoxythymidine exhibited cytotoxic effect exclusively toward HeLa cancer cell line, but not toward the normal HEK293 cells. Also, investigated compounds did not exhibit any antibacterial or antifungal activity at a concentration of 40 mM. The obtained results suggest that the presence of cytosine base is desirable for the appearance of cytotoxic effect, while the structural variations of the sugar ring play a minor role. Future modification of 2âČ-amino-2âČ-deoxythymidine could be a promising way to obtain more active anticancer substances