# Fluorescent Nucleosides and Oligonucleotides

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $380,418

## Abstract

PROJECT SUMMARY
 The goal of the proposed program is to design and synthesize new emissive nucleoside and nucleotide
analogs and implement them as probes for monitoring nucleoside- and nucleotide-based transformations as
well as nucleic acids function, structure, dynamics and recognition. Advancing effective fluorescence-based
tools for exploring nucleoside, nucleotide and oligonucleotides, as well as their metabolism, regulatory
processes and interactions with potential therapeutic agents will further knowledge and advance new
diagnostic approaches, facilitating drug discovery. Specifically, we will address:
 AIM 1. To design, synthesize and incorporate new isomorphic fluorescent nucleoside and
nucleotides. The main design criteria include: (i) High structural similarity to the native nucleobases to
faithfully mimic their size and shape, as well as hybridization and recognition properties, (ii) Red shifted
absorption spectrum to minimize overlap with the absorption of the natural bases, and (iii) Adequate emission
quantum efficiency and visible emission wavelengths. Efficient synthetic and enzymatic pathways will be
devised, providing the nucleosides, nucleotides and oligonucleotide.
 AIM 2. To photophysically and biophysically characterize the modified nucleosides and
oligonucleotides. The photophysical characteristics (e.g., absorption and emission maxima, quantum yield
and brightness, excited state lifetime, as well as susceptibility to environmental polarity and static and dynamic
quenching by native nucleosides) will be rigorously evaluated and interpreted. The outcome of these analyses
and the data generated dictate the utility and potential applications of the nucleoside surrogates.
 AIM 3. To implement the promising emissive analogs in biophysical, biochemical and discovery
assays. These assays will facilitate: (i) Studying the enzymatic deamination of adenosine to inosine, which
occurs in three key biological contexts: purine metabolism, mRNA editing and tRNA maturation; (ii)
Investigating the enzymatic synthesis of emissive second messengers, such as c-di-NMPs, and their
interactions with riboswitches and proteins (e.g., STING), (iii) Monitoring RNA–protein binding (e.g., k-
turn/7LAe) and translational events, including programmed ribosomal frameshifting, which could be detrimental
to native protein synthesis, but, when programmed (e.g., in viral replication) can maximize protein expression.
 Nucleic acids play central roles in cellular events and, as such, have immense impact on the emergence of
diseases and, in turn, on human health. This necessitates the development of new effective tools for studying
their recognition properties and alteration by exogenous agents. The emissive nucleoside analogs designed
and prepared will be implemented in novel real time fluorescence-based assays. These investigations will
further the fundamental understanding of key biological processes related to disease development and will
have long-term impa...

## Key facts

- **NIH application ID:** 9908107
- **Project number:** 5R01GM069773-16
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** YITZHAK TOR
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $380,418
- **Award type:** 5
- **Project period:** 2004-01-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9908107

## Citation

> US National Institutes of Health, RePORTER application 9908107, Fluorescent Nucleosides and Oligonucleotides (5R01GM069773-16). Retrieved via AI Analytics 2026-05-30 from https://api.ai-analytics.org/grant/nih/9908107. Licensed CC0.

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