# Cyclopropenones to assemble, analyze, and activate biomolecules

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2020 · $276,792

## Abstract

Project Summary
Chemical tools can provide unique insights into biomolecule structure and function. Included in this group
are bioorthogonal chemical reporters—biocompatible functional groups that can target diverse classes of
biomolecules and be selectively ligated with various probes. These reporters and reactions enable
biomolecules to be analyzed in their native environments. Despite their past successes and continued
potential, most chemical reporters have been slow to transition to biological studies and the scientific
community at large. Many reporters are too large or insufficiently stable for routine cellular use, or lack
chemical versatility. The long-term goal of our work is to develop robust, easy-to-access chemical probes
for tracking and controlling biomolecules in cells and tissues. The objective of this application is to develop
one reagent—cyclopropenone—as a general and versatile chemical reporter. Cyclopropenones harbor
unique features for biological application. They are small, reactive with bioorthogonal soft nucleophiles
(e.g., phosphines), and highly tunable. In addition to tagging biomolecules, cyclopropenones can be used
to control biomolecule function via phosphine-mediated crosslinking and decaging chemistries. Thus, from a
single cyclopropenone unit, one—in theory—can assemble, analyze, and activate biomolecules of interest.
The versatility and accessibility of such reagents can provide a “one-stop-shop” for tool users, bringing
chemical probes more rapidly into the hands of non-specialists. Guided by strong preliminary data, our
work will encompass the following specific aims: 1) Tune cyclopropenone reactivity for broad-spectrum
biomolecule analyses; (2) Exploit “latent” cyclopropenone reactivities for biomolecule assembly; and (3)
Establish chemical triggers of biomolecule function. Under the first aim, we will examine the scope of the
cyclopropenone-phosphine ligation, and identify scaffolds with suitable stability and reactivity profiles. In the
second aim, we will capitalize on “latent” cyclopropenone reactivities to assemble biomolecule conjugates.
In the third aim, we will develop cyclopropenone triggers that can be used to crosslink and activate
biomolecules of interest. Our approach is highly innovative, as it capitalizes on a unique reaction
mechanism to access multi-functional bioorthogonal properties. The proposed research is significant, as it
will provide versatile, easy-to-use chemical tools that are applicable to a broad spectrum of biomedical
research. The probes will also enable experiments not possible with existing toolsets. Additionally, like
other chemical technologies, the proposed reagents will likely inspire new discoveries in diverse fields.

## Key facts

- **NIH application ID:** 9822981
- **Project number:** 5R01GM126226-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Jennifer Prescher
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $276,792
- **Award type:** 5
- **Project period:** 2017-12-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9822981

## Citation

> US National Institutes of Health, RePORTER application 9822981, Cyclopropenones to assemble, analyze, and activate biomolecules (5R01GM126226-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9822981. Licensed CC0.

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