Convenient synthesis of pyrimidine 2′-deoxyribonucleoside monophosphates with important epigenetic marks at the 5-position. Issue 27 (25th June 2020)

• Record Type: Journal Article
• Authors: Zheng, Song; Tran, Ai; Curry, Alyson M.; White, Dawanna S.; Cen, Yana
• Is Part Of: Organic & biomolecular chemistry. Volume 18:Issue 27(2020)
• Page Start: 5164
• Page End: 5173
• Publication Date: 2020-06-25
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/d0ob00884b
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : A novel and concise chemo-enzymatic approach has been developed for the synthesis of epigenetically important pyrimidine 2′-deoxyribonucleoside monophosphates. Abstract : Methyl groups of thymine and 5-methylcytosine (5 m C) bases in DNA undergo endogenous oxidation damage. Additionally, 5 m C residues can be enzymatically deaminated or oxidized through either genetic alterations or the newly identified epigenetic reprogramming pathway. Several methods have been developed to measure the formation of modified DNA nucleobases including 32 P-postlabeling. However, the postlabeling method is often limited by the absence of authentic chemical standards. The synthesis of monophosphate standards of nucleotide oxidation products is complicated by the presence of additional functional groups on the modified bases that require complex protection and deprotection strategies. Due to the emerging interest in the pyrimidine oxidation products, the corresponding protected 3′-phosphoramidites needed for solid-phase oligonucleotide synthesis have been reported, and several are commercially available. We report here an efficient synthesis of 3′-monophosphates from 3′-phosphoramidites and the subsequent enzymatic conversion of 3′-monophosphates to the corresponding 5′-monophosphates using commercially available enzymes.