# Photoelectrocyclizations to Virulence Inhibiting Natural Product

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2021 · $8,388

## Abstract

Supplemental Funding Request for Photochemical Electrocyclizations to
 Virulence Inhibiting Natural Products
 Project Summary
Abstract of R01 GM132531. Reports of the increasing prevalence of drug resistant
bacteria has resulted in a vital need for new strategies for the development of
antimicrobials. This application offers such an approach. We plan to take advantage of
the enhanced understanding of the role that communication plays in bacterial virulence to
develop small molecules that interrupt this phenomenon. Specifically, this work is focused
on developing structurally and biologically interesting small molecule natural products from
the discorhabdin and abietane families as virulence inhibitors. As part of our effort to
generate these families we are developing new chemistry centered around photochemical
electrocyclization reactions including enantioselective transformations.
Request:
 We are requesting funds for salary support for Ms. Drue Domagala to carry out
research in the Rainier group for the summer of 2021. Ms. Domagala will be carrying out
research on the development of selective TLR-PROTAC systems as a means of targeting
the immune response to diseases including COVID and bacterial infections.
Summary:
 There are 10 structurally related Toll-Like Receptors (TLR’s) that are known in
humans. The TLR’s are involved in the immune response to injury and insult through their
ability to recognize pathogens (lipopeptides and proteins, RNA, lipids, flagellin, DNA, small
molecules, etc.). The immune response to these pathogens, while necessary, can become
uncontrolled. These unfortunate events happen across nearly all diseases and when it
does it can problematic. We propose that the development of selective inhibitors of TLR’s
may lead to the improved response to disease including bacterial infections and COVID.
We propose to synthesize and develop PROTAC inhibitors that consist of known pyrazole
ligands that have shown selectivity for various TLR’s with the E3 ligase inhibitor
thalidomide.

## Key facts

- **NIH application ID:** 10393381
- **Project number:** 3R01GM132531-03S1
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** JON Douglas RAINIER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $8,388
- **Award type:** 3
- **Project period:** 2019-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10393381

## Citation

> US National Institutes of Health, RePORTER application 10393381, Photoelectrocyclizations to Virulence Inhibiting Natural Product (3R01GM132531-03S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10393381. Licensed CC0.

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