Enzymatic Incorporation of Modified Purine Nucleotides in DNA. (14th November 2017)

• Record Type: Journal Article
• Authors: Abu El Asrar, Rania; Margamuljana, Lia; Abramov, Mikhail; Bande, Omprakash; Agnello, Stefano; Jang, Miyeon; Herdewijn, Piet
• Is Part Of: Chembiochem. Volume 18:Number 24(2017)
• Page Start: 2408
• Page End: 2415
• Publication Date: 2017-11-14
• Subjects: base-pair recognition -- DNA incorporation -- nucleic acids -- nucleosides -- synthetic biology; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201700393
• Languages: English
• ISSNs: 1439-4227

Abstract

Abstract: A series of nucleotide analogues, with a hypoxanthine base moiety (8‐aminohypoxanthine, 1‐methyl‐8‐aminohypoxanthine, and 8‐oxohypoxanthine), together with 5‐methylisocytosine were tested as potential pairing partners of N 8 ‐glycosylated nucleotides with an 8‐azaguanine or 8‐aza‐9‐deazaguanine base moiety by using DNA polymerases (incorporation studies). The best results were obtained with the 5‐methylisocytosine nucleotide followed by the 1‐methyl‐8‐aminohypoxanthine nucleotide. The experiments demonstrated that small differences in the structure (8‐azaguanine versus 8‐aza‐9‐deazaguanine) might lead to significant differences in recognition efficiency and selectivity, base pairing by Hoogsteen recognition at the polymerase level is possible, 8‐aza‐9‐deazaguanine represents a self‐complementary base pair, and a correlation exists between in vitro incorporation studies and in vivo recognition by natural bases in Escherichia coli, but this recognition is not absolute (exceptions were observed). Abstract : How will I recognize you? N 8 ‐Glycosylated nucleosides (with an 8‐azaguanine or 8‐aza‐9‐deazaguanine base moiety) are recognized by DNA polymerases for pairing with 5‐methylisocytosine or 8‐substituted hypoxanthine bases. The N 9 atom of the N 8 ‐linked nucleosides significantly affects base‐pair recognition, selective pairing (against recognition by natural bases), and the ability of the N 8 ‐nucleosides to form a self‐complementary pair.