- Spiroiminodihydantoin as an oxo-atom transfer product of 8-oxo-2-deoxyguanosine oxidation by chromium(V)
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(Chemical Equation Presented) Oxidation of the DNA lesion 8-oxo-2′-deoxyguanosine by the two electron oxidants N,N′- ethylenebis(salicylideneanimato)oxochromium(V) (Cr(V)-salen) and bis(2-ethyl-2-hydroxybutyrato)oxochromium(V) (Cr(V)-ehba) at neutral pH f
- Slade, Peter G.,Priestley, Nigel D.,Sugden, Kent D.
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- Structure-based design of guanosine analogue inhibitors targeting GTP cyclohydrolase IB towards a new class of antibiotics
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GTP cyclohydrolase (GCYH-I) is an enzyme in the folate biosynthesis pathway that has not been previously exploited as an antibiotic target, although several pathogens including N. gonorrhoeae use a form of the enzyme GCYH-IB that is structurally distinct from the human homologue GCYH-IA. A comparison of the crystal structures of GCYH-IA and -IB with the nM inhibitor 8-oxo-GTP bound shows that the active site of GCYH-IB is larger and differently shaped. Based on this structural information, we designed and synthesized a small set of 8-oxo-G derivatives with ether linkages at O6 and O8 expected to displace water molecules from the expanded active site of GCYH-IB. The most potent of these compounds, G3, is selective for GCYH-IB, supporting the premise that potent and selective inhibitors of GCYH-IB could constitute a new class of small molecule antibiotics.
- Haque, Ayesha,Hecht, David A.,Paranagama, Naduni,Purse, Byron W.,Samaan, George N.,Swairjo, Manal A.
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supporting information
(2019/12/09)
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- Oxidation of 9-β-d-ribofuranosyl uric acid by one-electron oxidants versus singlet oxygen and its implications for the oxidation of 8-oxo-7,8-dihydroguanosine
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Uric acid, a cellular antioxidant, undergoes oxidation in the presence of one-electron oxidants as well as singlet oxygen. In the present work, the oxidation pathways and products formed from oxidation of the uric acid nucleoside are compared to the more commonly studied uric acid free base. A wider distribution of products, including allantoin, urea, caffolide, and 5-carboxamido-5-hydroxyhydantoin nucleosides, are formed when the N9 position of uric acid is glycosylated. The oxidation pathways share some features in common with the oxidation of 8-oxo-7,8-dihydroguanosine, but the additional spectrum of products implies that the combination of oxidative and deaminative damage to guanosine may lead to a more complex set of DNA lesions than originally described.
- Nguyen, Khiem V.,Muller, James G.,Burrows, Cynthia J.
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supporting information; scheme or table
p. 2176 - 2180
(2011/05/05)
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- Reactivity toward singlet oxygen of a 7,8-dihydro-8-oxoguanosine ('8-hydroxyguanosine') formed by photooxidation of a guanosine derivative
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Total quenching (k(r) ± k(q)) and chemical reaction rates (k(r)) for the removal of singlet oxygen by 2',3',5'-tris((tert-butyldimethylsilyl)oxy)guanosine (1) and its oxidation product, 2',3',5'-tris((tert-butyldimethylsilyl)oxy)-7,8-dihydro-8-oxoguanosine (2), were determined by the time-resolved infrared luminescence technique and competition experiments, respectively. Compound 2 is two orders of magnitude more reactive with singlet oxygen than 1. A mechanism for the formation of 2 from 1 with singlet oxygen is proposed.
- Sheu,Foote
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p. 6439 - 6442
(2007/10/02)
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- 8-Substituted guanosine and 2'-deoxyguanosine derivatives as potential inducers of the differentiation of Friend erythroleukemia cells
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A variety of 8-substituted guanosine and 2'-deoxyguanosine derivatives were synthesized and tested as inducers of the differentiation of Friend murine erythroleukemia cells in culture. The most active agents in the guanosine series were 8-substituted -N(CH3)2, -NHCH3, -NH2, -OH, and -SO2CH3, which caused 68, 42, 34, 33, and 30% of erythroleukemia cells to attain benzidine positivity, a functional measure of maturation, at concentrations of 5, 1, 0.4, 5, and 5 mM, respectively. The 8-OH derivative of the 2'-deoxyguanosine series produced comparable activity, causing 62% benzidine-positive cells at a level of 0.2 mM. These findings indicate that 8-substituted analogues of guanosine and 2'-deoxyguanosine have the potential to terminate leukemia cell proliferation through conversion to end-stage differentiated cells.
- Lin,Cheng,Ishiguro,Sartorelli
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p. 1194 - 1198
(2007/10/02)
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