# Conditional Control of Drug Function Through α-Boryl Ether Oxidation

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2022 · $384,484

## Abstract

Project Summary
The objective of this proposal is to design new agents that release biological effectors in the presence of
hydrogen peroxide, providing an approach to spatially precise strategies for treating a multitude of medical
conditions that are characterized by oxidative stress. These conditions include, but are not limited to,
reperfusion injury, viral infection, neurodegeneration, traumatic brain injury, and cancer. Spatially precise
release will be beneficial because it can minimize general drug exposure, allowing for lower doses while
mitigating side effects. The new agents are based on the hydrogen peroxide mediated conversion of α-boryl
ethers and related structures to hemiacetals, leading to a breakdown that forms a ketone and releases the
effector. The ketone by-products that are released in this approach are non-toxic, providing excellent
opportunities to treat diseases in which the promotion of cellular responses, rather than cell death, is the
objective. This multidisciplinary program will utilize organic synthesis, kinetics studies, cellular assays, and
animal studies to achieve its objectives. The first Specific Aim is to devise agents that release cyclic
dinucleotides under oxidative conditions in an effort to stimulate an immune response against tumors. The
second Specific Aim is to merge drug release with radiation therapy to create a site-specific approach to
cancer treatment. Releasing agents that mimic the physiological response to radiation will allow for an
autoinductive release mechanism that lowers the required radiation dose and minimizes late stage side effects.
The combination of the skills of the PIs and collaborators on these projects creates unique opportunities for
localized disease treatment while providing guidance for developing a general strategy for designing prodrugs
that release structurally disparate agents.

## Key facts

- **NIH application ID:** 10380804
- **Project number:** 5R01GM127153-04
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Alexander Deiters
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $384,484
- **Award type:** 5
- **Project period:** 2019-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10380804

## Citation

> US National Institutes of Health, RePORTER application 10380804, Conditional Control of Drug Function Through α-Boryl Ether Oxidation (5R01GM127153-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10380804. Licensed CC0.

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