Synthesis and photophysical characterization of a pH-sensitive quadracyclic uridine (qU) analogue
Journal article, 2024

Fluorescent base analogues (FBAs) have become useful tools for applications in biophysical chemistry, chemical biology, live-cell imaging, and RNA therapeutics. Herein, two synthetic routes towards a novel FBA of uracil named qU (quadracyclic uracil/uridine) are described. The qU nucleobase bears a tetracyclic fused ring system and is designed to allow for specific Watson-Crick base pairing with adenine. We find that qU absorbs light in the visible region of the spectrum and emits brightly with a quantum yield of 27 % and a dual-band character in a wide pH range. With evidence, among other things, from fluorescence lifetime measurements we suggest that this dual emission feature results from an excited-state proton transfer (ESPT) process. Furthermore, we find that both absorption and emission of qU are highly sensitive to pH. The high brightness in combination with excitation in the visible and pH responsiveness makes qU an interesting native-like nucleic acid label in spectroscopy and microscopy applications in, for example, the field of mRNA and antisense oligonucleotide (ASO) therapeutics.

pH sensitivity

dual emission

uridine analog

FBA

fluorescence

Author

Hoang Ngoan Le

Chalmers, Chemistry and Chemical Engineering, Chemistry and Biochemistry

AstraZeneca AB

Jagannath Kuchlyan

Chalmers, Chemistry and Chemical Engineering, Chemistry and Biochemistry

Tom Baladi

AstraZeneca AB

Bo Albinsson

Chalmers, Chemistry and Chemical Engineering, Chemistry and Biochemistry

Anders Dahlén

AstraZeneca AB

Marcus Wilhelmsson

Chalmers, Chemistry and Chemical Engineering, Chemistry and Biochemistry

Chemistry - A European Journal

0947-6539 (ISSN) 1521-3765 (eISSN)

Vol. 30 18 e202303539

Funktionell leverans av nukleotid-baserade läkemedel

Swedish Foundation for Strategic Research (SSF) (IRC15-0065), 2017-03-01 -- 2024-12-31.

Subject Categories

Biological Sciences

Chemical Sciences

DOI

10.1002/chem.202303539

PubMed

38230625

More information

Latest update

4/6/2024 4