Caging of a Strongly Pairing Fluorescent Thymidine Analog with Soft Nucleophiles. Issue 8 (12th December 2022)

• Record Type: Journal Article
• Authors: Eyberg, Juri; Ringenberg, Mark; Richert, Clemens
• Is Part Of: Chemistry. Volume 29:Issue 8(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-12-12
• Subjects: caging -- DNA -- nucleosides -- nucleotides -- reporters; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.202203289
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: Controlling the pairing strength of nucleobases in DNA through reactions with compounds found inside the cell is a formidable challenge. Here we report how a thiazolyl substituent turns a strongly pairing ethynylpyridone C ‐nucleoside into a reactive residue in oligonucleotides. The thiazolyl‐bearing pyridone reacts with soft nucleophiles, such as glutathione, but not with hard nucleophiles like hydroxide or carbonate. The addition products pair much more weakly with adenine in a complementary strand than the starting material, and also change their fluorescence. This makes oligonucleotides containing the new deoxynucleoside interesting for controlled release. Due to its reactivity toward N, P, S, and Se ‐nucleophiles, and the visual signal accompanying chemical conversion, the fluorescent nucleotide reported here may also have applications in chemical biology, sensing and diagnostics. Abstract : Releasing the base pairing partner : A pyridone C ‐nucleoside is reported that binds very tightly to adenine as complementary base. Upon exposure to soft nucleophiles, such as glutathione or selenocysteine, the new base reacts and releases its grip on the base pairing partner, allowing for the dissociation of duplexes. At the same time, the C ‐nucleoside changes its fluorescence signature, providing a visual signal for the transformation.