# Fluorescent nucleosides, nucleotides and oligonucleotides

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $468,960

## Abstract

PROJECT SUMMARY
 Nucleic acids and their building blocks play central roles in all cellular events and, as such, have immense
impact on the emergence of diseases and, in turn, on human health. Studying such events is complicated by
the non-emissive nature of the natural nucleobases, which frequently deprives researchers from the use of
modern fluorescence-based techniques. Faithful minimally perturbing emissive nucleoside surrogates can thus
facilitate the monitoring of nucleoside, nucleotides and nucleic acids-based transformations at nucleoside/tide-
“resolution”, and advance basic research, diagnostic tools and drug discovery efforts.
 The goal of the proposed program is to design and synthesize new isomorphic 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. Specifically, major
contemporary challenges will be tackled in an attempt to bridge major gaps, among them: (a) Powerful
biophysical techniques, such as Fluorescence-Detected Circular Dichroism (FDCD), introduced nearly five
decades ago, remains practically unexplored; (b) Multiphoton, imaging and single molecule spectroscopy-
based experiments, using native or minimally perturbed oligonucleotides or nucleotide cofactors, are severely
underutilized; (c) Similarly, single molecule enzymology of nucleoside/tide processing enzymes has not
advanced; (d) Probes for real time exploration of fundamental processes such as peptidyl transferase, phase
separated membrane-less organelle formation and mRNA decay are lacking; (e) Nucleoside/tide-based
metabolic processes and nucleotide-based signaling events cannot be directly monitored; and (f) High
throughput screening for nucleosides and nucleosides processing enzymes cannot be performed in real-time
and in a high throughput manner without the use of faithful emissive surrogate substrates.
 Capitalizing on several useful families of emissive nucleoside surrogates developed in our laboratory, we
will further refine our “designer” emissive and isomorphic nucleosides/tides and apply them to advance
solutions to the challenges articulated above. We will pursue the advancement of new physical and
biochemical methods, as well as effective real-time screening and diagnostic tools. These efforts will expand
the community's arsenal of emissive functional probes, driving future strides into discovery and imaging
applications. These innovations, in turn, will further fundamental understanding of key biological processes
related to disease development and will have long-term impact on improving human health.

## Key facts

- **NIH application ID:** 10083552
- **Project number:** 1R35GM139407-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** YITZHAK TOR
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $468,960
- **Award type:** 1
- **Project period:** 2021-02-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10083552

## Citation

> US National Institutes of Health, RePORTER application 10083552, Fluorescent nucleosides, nucleotides and oligonucleotides (1R35GM139407-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10083552. Licensed CC0.

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