High Fidelity Enzyme‐Free Primer Extension with an Ethynylpyridone Thymidine Analog. Issue 64 (8th October 2021)

• Record Type: Journal Article
• Authors: Han, Jianyang; Kervio, Eric; Richert, Clemens
• Is Part Of: Chemistry. Volume 27:Issue 64(2021)
• Page Start: 15918
• Page End: 15921
• Publication Date: 2021-10-08
• Subjects: antivirals -- C-nucleosides -- genetic copying -- nucleotides -- replication; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.202102996
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: High fidelity base pairing is important for the transmission of genetic information. Weak base pairs can lower fidelity, complicating sequencing, amplification and replication of DNA. Thymidine 5′‐monophosphate (TMP) is the most weakly pairing nucleotide among the canonical deoxynucleotides, causing high errors rates in enzyme‐free primer extension. Here we report the synthesis of an ethynylpyridone C ‐nucleoside analog of 3′‐amino‐2′, 3′‐dideoxythymidine monophosphate and its incorporation in a growing strand by enzyme‐free primer extension. The ethynylpyridone C ‐nucleotide accelerates extension more than five‐fold, reduces misincorporation and readily displaces TMP in competition experiments. The results bode well for the use of the C ‐nucleoside as replacements for thymidine in practical applications. Abstract : Strongly binding analog : When thymidine is replaced with ethynylmethylpyridone, enzyme‐free genetic copying occurs faster and with higher fidelity.