# Toolkit for Fast, Multipurpose and Inducible Bioorthogonal Chemistry

> **NIH NIH R01** · UNIVERSITY OF DELAWARE · 2020 · $358,800

## Abstract

Project Summary
The goal of this proposal will be to develop a diverse set of new chemical tools centered
on tetrazine ligation– the fastest known bioorthogonal reaction. This proposal describes
new tools for the safe synthesis and direct coupling of `minimalist' tetrazines to any
molecule of interest, including API's and fluorescent reporters. We also propose to
develop specialized tetrazines that can serve a dual role in enabling protein purification
followed by subsequent site-selective bioorthogonal chemistry. Finally, we propose to
develop efficient catalytic methods for `turning on' rapid bioorthogonal chemistry in
cellular context. We will develop tool molecules with high stability in the cellular
environment in their `off' state, and the fastest bioorthogonal reactions to date in their `on'
state. An application of the catalytically inducible tetrazine ligation is new method of
drug release where a photocatalyst-antibody conjugate is pretargeted to a disease site,
and red light is used to drive the local release of a cytotoxic reagent from a photocaged
prodrug.

## Key facts

- **NIH application ID:** 9899272
- **Project number:** 5R01GM132460-02
- **Recipient organization:** UNIVERSITY OF DELAWARE
- **Principal Investigator:** JOSEPH M FOX
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $358,800
- **Award type:** 5
- **Project period:** 2019-04-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9899272

## Citation

> US National Institutes of Health, RePORTER application 9899272, Toolkit for Fast, Multipurpose and Inducible Bioorthogonal Chemistry (5R01GM132460-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9899272. Licensed CC0.

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