Beilstein J. Org. Chem.2024,20, 1088–1098, doi:10.3762/bjoc.20.96
development of more potent CDA and APOBEC3 inhibitors.
Keywords: APOBEC3; cytidine deaminase; enzyme activity; inhibitor; nucleoside; nucleotide; zebularine; Introduction
Spontaneous hydrolytic deamination of cytosine to uracil (Figure 1A) is very slow under ambient conditions [1], but it is greatly
been synthesised in the past and evaluated as inhibitors targeting the active site of CDA. THU (Ia) [45][48], zebularine (Z, IIa) [47][49][50] and 5-fluorozebularine (FZ, IIb) [47][51] as well as diazepinone riboside (IIIa) [42][43][44][52] were among the most potent compounds (Figure 1B). THU (Ia
have recently developed the first rationally designed competitive inhibitors of A3 by incorporating 2'-deoxy derivatives of zebularine, i.e., 2'-deoxyzebularine (dZ, IIc) and 5-fluoro-2'-deoxyzebularine (FdZ, IId, Figure 1B) [54] as well as diazepinone 2'-deoxyriboside (IIIb) [55] into DNA fragments
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Graphical Abstract
Figure 1:
A) Deamination of cytosine, dC and C as individual nucleosides or as part of a polynucleotide chain...