# Hydrogen Sulfide and Carbonyl Sulfide Delivery for Biological Applications

> **NIH NIH R01** · UNIVERSITY OF OREGON · 2022 · $295,412

## Abstract

Project Summary
Hydrogen sulfide (H2S) plays important roles in human health ranging from vascular biology to tissue
regeneration. To advance investigations into roles, researchers often use H2S donors to directly modulate sulfide
levels during experiments. Despite this broad utility, key unmet needs remain that will be addressed in this
proposal. The long-term goal of this research is to develop and deploy COS/H2S donors to investigate and
advance the multifaceted roles of reactive sulfur species related to human health. The overall objectives of this
proposal are to broaden the platform of COS/H2S releasing motifs, to understand how different CA isoforms
impact COS to H2S conversion, and to apply COS/H2S donors to in vivo models of bone regeneration. The
rationale for these studies is that the functional tools for COS/H2S delivery and a greater understanding of
differential CA isoform activity toward COS hydrolysis will enable future applications in which COS/H2S release
is targeted to systems where key CA isoforms are present and H2S is known to play a protective effect. The
proposed investigations include three specific aims: (1) Expansion, refinement, and application of COS/H2S
releasing platforms; (2) Investigation in to the differential CA isoform activity toward COS hydrolysis; and (3)
Application of COS/H2S donors to bone regeneration. This proposal builds from prior work establishing that COS
releasing molecules can function as H2S donors due to the rapid enzymatic conversion of COS to H2S by
carbonic anhydrase (CA). In Aim 1, new chemical approaches are used to enable COS/H2S delivery, expand the
dynamic range and palette of traceable COS/H2S donors, and provide amplified release. In Aim 2, the hydrolytic
activity of individual CA isoforms toward COS and model thioester/thionoester substrates are investigated to
understand isoform differences in CA efficiency toward COS hydrolysis. In Aim 3, the developed COS/H2S
donors are used to investigate the role of H2S in cell and animal models of bone regeneration. This approach is
innovative because it provides new approaches to COS/H2S delivery that address key unmet needs in the field
and provides the first insights into the differential activity of CA isoforms for COS to H2S conversion. Moreover,
the proposed applications in bone regeneration are innovative because they not only leverage the protective
effects of H2S and high local activity of CA during osteogenesis, but also leverages the underutilized connection
of H2S with Ca2+ recruitment in osteoclasts. The proposed research is significant because it provides new
approaches that directly address key limitations in the field, including amplified release systems, trackable
donors, and analyte replacement methodologies. In addition, the proposed research provides the first insights
into CA isoform differences for COS to H2S conversion, which will be leveraged in model systems relevant to
human health in which both CA activity and H2S deli...

## Key facts

- **NIH application ID:** 10474265
- **Project number:** 5R01GM113030-07
- **Recipient organization:** UNIVERSITY OF OREGON
- **Principal Investigator:** Michael Pluth
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $295,412
- **Award type:** 5
- **Project period:** 2015-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10474265

## Citation

> US National Institutes of Health, RePORTER application 10474265, Hydrogen Sulfide and Carbonyl Sulfide Delivery for Biological Applications (5R01GM113030-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10474265. Licensed CC0.

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