Synthesis and photophysical characterization of fluorescent indole nucleoside analogues

Jacob M Sawyer; Kellan T Passow; Daniel A Harki

doi:10.1039/d3ra03457g

Synthesis and photophysical characterization of fluorescent indole nucleoside analogues

RSC Adv. 2023 May 31;13(24):16369-16376. doi: 10.1039/d3ra03457g. eCollection 2023 May 30.

Authors

Jacob M Sawyer¹, Kellan T Passow², Daniel A Harki^{1

2}

Affiliations

¹ Department of Chemistry, University of Minnesota Minneapolis Minnesota 55455 USA daharki@umn.edu.
² Department of Medicinal Chemistry, University of Minnesota Minneapolis Minnesota 55455 USA.

Abstract

Fluorescent nucleosides are useful chemical tools for biochemical research and are frequently incorporated into nucleic acids for a variety of applications. The most widely utilized fluorescent nucleoside is 2-aminopurine-2'-deoxyribonucleoside (2APN). However, 2APN is limited by a moderate Stokes shift, molar extinction coefficient, and quantum yield. We recently reported 4-cyanoindole-2'-deoxyribonucleoside (4CIN), which offers superior photophysical characteristics in comparison to 2APN. To further improve upon 4CIN, a focused library of additional analogues combining the structural features of 2APN and 4CIN were synthesized and their photophysical properties were quantified. Nucleosides 2-6 were found to possess diverse photophysical properties with some features superior to 4CIN. In addition, the structure-function relationship data gained from 1-6 can inform the design of next-generation fluorescent indole nucleosides.