Cytidine deaminase can deaminate fused pyrimidine ribonucleosides. Issue 28 (21st May 2021)

• Record Type: Journal Article
• Authors: Ludford, Paul T.; Li, Yao; Yang, Shenghua; Tor, Yitzhak
• Is Part Of: Organic & biomolecular chemistry. Volume 19:Issue 28(2021)
• Page Start: 6237
• Page End: 6243
• Publication Date: 2021-05-21
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/d1ob00705j
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : Cytidine deaminase effectively deaminates three emissive fused cytidine analogues and the reactions can be monitored in real time by fluorescence. 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.