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However, APOBEC3\u2010mediated mutagenesis of viral and cancer DNA promotes its evolution, thus enabling disease progression and the development of drug resistance. Therefore, APOBEC3 inhibition offers a new strategy to complement existing antiviral and anticancer therapies by making such therapies effective for longer periods of time, thereby preventing the emergence of drug resistance. Here, we have synthesised 2\u2032\u2010deoxynucleoside forms of several known inhibitors of cytidine deaminase (CDA), incorporated them into oligodeoxynucleotides (oligos) in place of 2\u2032\u2010deoxycytidine in the preferred substrates of APOBEC3A, APOBEC3B, and APOBEC3G, and evaluated their inhibitory potential against these enzymes. An oligo containing a 5\u2010fluoro\u20102\u2032\u2010deoxyzebularine (5FdZ) motif exhibited an inhibition constant against APOBEC3B 3.5\u2005times better than that of the comparable 2\u2032\u2010deoxyzebularine\u2010containing (dZ\u2010containing) oligo. A similar inhibition trend was observed for wild\u2010type APOBEC3A. In contrast, use of the 5FdZ motif in an oligo designed for APOBEC3G inhibition resulted in an inhibitor that was less potent than the dZ\u2010containing oligo both in the case of APOBEC3G<jats:sub>CTD<\/jats:sub> and in that of full\u2010length wild\u2010type APOBEC3G.<\/jats:p>","DOI":"10.1002\/cbic.201900505","type":"journal-article","created":{"date-parts":[[2019,10,21]],"date-time":"2019-10-21T06:19:42Z","timestamp":1571638782000},"page":"1028-1035","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Differential Inhibition of APOBEC3 DNA\u2010Mutator Isozymes by Fluoro\u2010 and Non\u2010Fluoro\u2010Substituted 2\u2032\u2010Deoxyzebularine Embedded in Single\u2010Stranded DNA"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3592-0336","authenticated-orcid":false,"given":"Maksim V.","family":"Kvach","sequence":"first","affiliation":[{"name":"School of Fundamental Sciences Massey University  Private Bag 11\u2009222 Palmerston North 4442 New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8788-9516","authenticated-orcid":false,"given":"Fareeda M.","family":"Barzak","sequence":"additional","affiliation":[{"name":"School of Fundamental Sciences Massey University  Private Bag 11\u2009222 Palmerston North 4442 New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Harjes","sequence":"additional","affiliation":[{"name":"School of Fundamental Sciences Massey University  Private Bag 11\u2009222 Palmerston North 4442 New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry A. 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