Work

Sequence-specific fluorescence turn-on arises from base pairing-templated tautomerism in the tricyclic cytidine analogue DEA tC

Year: 2025

Type: article

Abstract: tC exhibit up to a fivefold fluorescence increase upon hybrid duplex formation and base pairing with G, and a lesser degree of fluorescence turn-on when base pairing with inosine. Other purine nucleobases do not induce significant fluorescence turn-on. Solvent kinetic isotope effect measurements, excitation-emission matrix (EEM) analysis, and spectral comparisons indicate that fluorescence turn-on originates from base pairing-templated tautomerism. The non-emissive T-like form predominates in the single strand and in duplexes paired with A, whereas the emissive C-like tautomer is selectively stabilized upon duplex formation when paired with G. Density functional theory (DFT) calculations further support this tautomeric control model. Although base stacking influences overall brightness, it does not alter the mechanism or specificity of fluorescence turn-on. Modulation of emission through tautomeric control offers a powerful strategy for designing nucleobase analogues with base pairing-specific fluorescence responses.

Source: RSC Chemical Biology

DOI: 10.1039/d5cb00243e

Authors: Ana Shalamberidze, Harrison R. Pearce, Andrew L. Cooksy, Byron W. Purse

Institution: San Diego State University

Language: English

Topic: DNA and Nucleic Acid Chemistry

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $1,962

Funders: National Science Foundation, Office of Advanced Cyberinfrastructure, Division of Chemistry