# A subcellularly targeted photocaged inhibitor for mitochondrial carbonic anhydrase V

**Authors:** Noushaba Nusrat Mafy, Kanchan Aggarwal, Sky Price, Dorothea B. Hudson, Elva Ye, Divya Kolli, Emily L. Que

PMC · DOI: 10.1039/d5dt01161b · Dalton Transactions (Cambridge, England : 2003) · 2025-07-04

## TL;DR

This paper introduces a light-activated inhibitor that specifically targets a mitochondrial enzyme linked to obesity, allowing precise control over its activity.

## Contribution

The first photoactivatable inhibitor designed to target mitochondrial carbonic anhydrase V with subcellular precision.

## Key findings

- The inhibitor uses a coumarin cage and pyridinium group for mitochondrial targeting and light-controlled activation.
- Light exposure enables spatial and temporal inhibition of mitochondrial CA-V activity.
- The approach combines subcellular targeting with photoresponsive chemistry to modulate enzyme function.

## Abstract

We report the first photoactivatable inhibitor specifically targeting mitochondrial CA-V, a promising anti-obesity target. It features a sulfonamide metal-binding group caged with a photoremovable coumarin and guided to mitochondria via a pyridinium moiety. Light exposure removes the cage, enabling precise spatial and temporal inhibition of mitochondrial CA-V activity.

Selective targeting of mitochondrial carbonic anhydrases using subcellular directing and photoresponsive protecting groups to mask zinc active site coordinating ligand.

## Linked entities

- **Chemicals:** sulfonamide (PubChem CID 5333), coumarin (PubChem CID 323), pyridinium (PubChem CID 4989215)
- **Diseases:** obesity (MONDO:0011122)

## Full-text entities

- **Genes:** CA5A (carbonic anhydrase 5A) [NCBI Gene 763] {aka CA5, CA5AD, CAV, CAVA, GS1-21A4.1}
- **Diseases:** obesity (MESH:D009765)
- **Chemicals:** sulfonamide (MESH:D013449), pyridinium (-), metal (MESH:D008670), coumarin (MESH:C030123)

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12226970/full.md

## References

52 references — full list in the complete paper: https://tomesphere.com/paper/PMC12226970/full.md

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Source: https://tomesphere.com/paper/PMC12226970