# Toolkit for Fast, Multipurpose and Inducible Bioorthogonal Chemistry

> **NIH NIH R01** · UNIVERSITY OF DELAWARE · 2023 · $493,511

## 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
a continued effort to develop new bioorthogonal reagents. Methods will be developed for
the safe synthesis and direct coupling of ‘minimalist’ tetrazines to any molecule of
interest, including chemical probes and fluorescent reporters. We also propose to
develop tetrazines that can serve as “affinity bioorthogonal chemistry” tags that can
serve a dual role in enabling protein purification followed by subsequent site-selective
bioorthogonal chemistry. Applications to on-resin protein-protein and protein-biomolecule
assembly are proposed. We propose to develop efficient catalytic methods for ‘turning
on’ rapid bioorthogonal chemistry in cellular context, providing tool molecules with high
stability in the cellular environment in their ‘off’ state, and the fastest bioorthogonal
reactions to date in their ‘on’ state. Efficient photocatalysts have been developed that
can target bioorthogonal turn-on in vivo and at the subcellular level. Near-IR
photocatalysts as well as thermal catalysts will be developed as will new enabling
technologies for studying protein dynamics and for proteomic target identification.
Finally, we will also develop bioorthogonal N-acylmuramic acid (NAM) and N-
acylglucosamine (NAG) molecules for use in probe applications in microbiology and
immunology research.

## Key facts

- **NIH application ID:** 10660115
- **Project number:** 2R01GM132460-05
- **Recipient organization:** UNIVERSITY OF DELAWARE
- **Principal Investigator:** JOSEPH M FOX
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $493,511
- **Award type:** 2
- **Project period:** 2019-04-01 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10660115

## Citation

> US National Institutes of Health, RePORTER application 10660115, Toolkit for Fast, Multipurpose and Inducible Bioorthogonal Chemistry (2R01GM132460-05). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10660115. Licensed CC0.

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