期刊
ACS CHEMICAL BIOLOGY
卷 16, 期 7, 页码 1208-1214出版社
AMER CHEMICAL SOC
DOI: 10.1021/acschembio.1c00232
关键词
-
资金
- National Institutes of Health [GM 069773]
This study investigates two emissive heterocyclic cores as surrogate GDA substrates, demonstrating a new guanine surrogate that can be used for real-time study of GDA and its inhibition.
Guanine deaminase (GDA) deaminates guanine to xanthine. Despite its significance, the study of human GDA remains limited compared to other metabolic deaminases. As a result, its substrate and inhibitor repertoire are limited, and effective real-time activity, inhibitory, and discovery assays are missing. Herein, we explore two emissive heterocyclic cores, based on thieno[3,4-d]pyrimidine (N-th) and isothiazole[4,3-d]pyrimidine (N-tz), as surrogate GDA substrates. We demonstrate that, unlike the thieno analog, (th)G(N), the isothiazolo guanine surrogate, (tz)G(N), does undergo effective enzymatic deamination by GDA and yields the spectroscopically distinct xanthine analog, X-tz(N). Further, we showcase the potential of this fluorescent nucleobase surrogate to provide a visible spectral window for a real-time study of GDA and its inhibition.
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