151566-06-2Relevant articles and documents
Structure-based design of guanosine analogue inhibitors targeting GTP cyclohydrolase IB towards a new class of antibiotics
Haque, Ayesha,Hecht, David A.,Paranagama, Naduni,Purse, Byron W.,Samaan, George N.,Swairjo, Manal A.
, (2019)
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.
Reactivity toward singlet oxygen of a 7,8-dihydro-8-oxoguanosine ('8-hydroxyguanosine') formed by photooxidation of a guanosine derivative
Sheu,Foote
, p. 6439 - 6442 (1995)
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.
