Issue 28, 2021

Cytidine deaminase can deaminate fused pyrimidine ribonucleosides

Abstract

The tolerance of cytidine deaminase (CDA) to expanded heterocycles is explored via three fluorescent cytidine analogues, where the pyrimidine core is fused to three distinct five-membered heterocycles at the 5/6 positions. The reaction between CDA and each analogue is followed by absorption and emission spectroscopy, revealing shorter reaction times for all analogues than the native substrate. Pseudo-first order and Michaelis–Menten kinetic analyses provide insight into the enzymatic deamination reactions and assist in drawing comparison to established structure activity relationships. Finally, inhibitor screening modalities are created for each analogue and validated with zebularine and tetrahydrouridine, two known CDA inhibitors.

Graphical abstract: Cytidine deaminase can deaminate fused pyrimidine ribonucleosides

Supplementary files

Article information

Article type
Paper
Submitted
12 Apr 2021
Accepted
05 May 2021
First published
11 May 2021

Org. Biomol. Chem., 2021,19, 6237-6243

Cytidine deaminase can deaminate fused pyrimidine ribonucleosides

P. T. Ludford, Y. Li, S. Yang and Y. Tor, Org. Biomol. Chem., 2021, 19, 6237 DOI: 10.1039/D1OB00705J

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