Synthesis of 1,4-azaphosphinine nucleosides and evaluation as inhibitors of human cytidine deaminase and APOBEC3A

• Maksim V. Kvach,
• Stefan Harjes,
• Harikrishnan M. Kurup,
• Geoffrey B. Jameson,
• Elena Harjes and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2024, 20, 1088–1098, doi:10.3762/bjoc.20.96

• of the University of Auckland, Level 2, 3A Symonds Street, Auckland 1142, New Zealand 10.3762/bjoc.20.96 Abstract Nucleoside and polynucleotide cytidine deaminases (CDAs), such as CDA and APOBEC3, share a similar mechanism of cytosine to uracil conversion. In 1984, phosphapyrimidine riboside was

• inhibition of APOBEC3A was observed for modified DNAs. Although this shows that the negative charge is poorly accommodated in the active site of CDA and APOBEC3, the synthetic route reported here provides opportunities for the synthesis of other derivatives of phosphapyrimidine riboside for potential

• 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