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The identification of biomolecules for disease diagnosis requires facile analytical technologies with high precision and reliability. Several signal transduction pathways have inspired the development of various bioanalytical systems. However, most systems are greatly limited by a single‐mechanism/mode assay, which easily results in false‐positive/negative results. Herein, a multiple‐mechanism‐driven optical biosensor for 8‐oxo‐2′‐deoxyguanosine (8‐oxo‐dG), an early pathological signature of DNA lesions and various diseases, is designed by assembling adenine as a recognition element, mellitic acid as energy donors and Eu3+ as signal reporters into one metal‐organic framework (MOF) system. Significantly, by regulating the delicate competition between the different mechanisms, the fabricated single platform (Eu‐ade‐MOF) concurrently provides two switchable approaches for rapid qualitative (30 s and 4 min) and quantitive (ppb level) recognition of 8‐oxo‐dG in both complex artificial and real human urine environments. Compared with those single‐mechanism/mode‐driven detections, this light‐operated dual‐mode analysis system can inherently boost the analysis reliability and largely minimize the chances of false negatives/positives for a non‐invasive diagnosis of DNA damage and related diseases. This work represents the first effort in designing a luminescent sensor coupling multiple mechanisms in a single interface to determine DNA damage degree and provides a new approach for developing multimode analysis platforms for human health monitoring. 相似文献
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Dr. Silvia Meneghesso Dr. Andrea Brancale Prof. Jan Balzarini Prof. Lieve Naesens Prof. Christopher McGuigan 《ChemMedChem》2013,8(3):415-425
2′‐Fluoro‐2′‐deoxyguanosine has been reported to have potent anti‐influenza virus activity in vitro and in vivo. Herein we describe the synthesis and biological evaluation of 6‐modified 2′‐fluoro‐2′‐deoxyguanosine analogues and their corresponding phosphoramidate ProTides as potential anti‐influenza virus agents. Whereas the parent nucleosides were devoid of antiviral activity in two different cellular assays, the 5′‐O‐naphthyl(methoxy‐L ‐alaninyl) ProTide derivatives of 6‐O‐methyl‐2′‐fluoro‐2′‐deoxyguanosine, 6‐O‐ethyl‐2′‐fluoro‐2′‐deoxyguanosine, and 2′‐deoxy‐2′‐fluoro‐6‐chloroguanosine, and the 5′‐O‐naphthyl(ethoxy‐L ‐alaninyl) ProTide of 6‐O‐ethyl‐2′‐fluoro‐2′‐deoxyguanosine displayed antiviral EC99 values of ~12 μM . The antiviral results are supported by metabolism studies. Rapid conversion into the L ‐alaninyl metabolite and then 6‐modified 2′‐fluoro‐2′‐deoxyguanosine 5′‐monophosphate was observed in enzymatic assays with yeast carboxypeptidase Y or crude cell lysate. Evidence for efficient removal of the 6‐substituent on the guanine part was provided by enzymatic studies with adenosine deaminase, and by molecular modeling of the nucleoside 5′‐monophosphates in the catalytic site of a model of ADAL1, thus indicating the utility of the double prodrug concept. 相似文献
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Mikhail S. Drenichev Vladimir E. Oslovsky Anastasia A. Zenchenko Claudia V. Danilova Mikhail A. Varga Roman S. Esipov Dmitry D. Lykoshin Cyril S. Alexeev 《International journal of molecular sciences》2022,23(5)
A comparative analysis of the transglycosylation conditions catalyzed by E. coli nucleoside phosphorylases, leading to the formation of 2′-deoxynucleosides, was performed. We demonstrated that maximal yields of 2′-deoxynucleosides, especially modified, can be achieved under small excess of glycosyl-donor (7-methyl-2′-deoxyguanosine, thymidine) and a 4-fold lack of phosphate. A phosphate concentration less than equimolar one allows using only a slight excess of the carbohydrate residue donor nucleoside to increase the reaction’s output. A three-step methodology was elaborated for the preparative synthesis of purine-modified 2′-deoxyribonucleosides, starting from the corresponding ribonucleosides. 相似文献
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