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Real-Time Monitoring of Human Guanine Deaminase Activity by an Emissive Guanine Analog
Author(s) -
Marcela S. Bucardo,
You Wu,
Paul T. Ludford,
Yao Li,
Andréa Fin,
Yitzhak Tor
Publication year - 2021
Publication title -
acs chemical biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.899
H-Index - 111
eISSN - 1554-8937
pISSN - 1554-8929
DOI - 10.1021/acschembio.1c00232
Subject(s) - guanine , deamination , xanthine , pyrimidine , isothiazole , hypoxanthine , chemistry , biochemistry , enzyme , nucleotide , medicinal chemistry , gene
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 ( th N ) and isothiazole[4,3- d ]pyrimidine ( tz N ), 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, tz X 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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