Synthesis and Pharmacological Characterization of New Photocaged Agonists for Histamine H<sub>3</sub> and H<sub>4</sub> Receptors
The modulation of biological processes with light-sensitive chemical probes promises precise temporal and spatial control. Yet, the design and synthesis of suitable probes is a challenge for medicinal chemists. This article introduces a photocaging strategy designed to modulate the pharmacology of h...
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| Main Authors: | , , , , |
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| Format: | Book |
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MDPI AG,
2024-04-01T00:00:00Z.
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| Online Access: | Connect to this object online. |
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| Summary: | The modulation of biological processes with light-sensitive chemical probes promises precise temporal and spatial control. Yet, the design and synthesis of suitable probes is a challenge for medicinal chemists. This article introduces a photocaging strategy designed to modulate the pharmacology of histamine H<sub>3</sub> receptors (H<sub>3</sub>R) and H<sub>4</sub> receptors (H<sub>4</sub>R). Employing the photoremovable group BODIPY as the caging entity for two agonist scaffolds-immepip and 4-methylhistamine-for H<sub>3</sub>R and H<sub>4</sub>R, respectively, we synthesized two BODIPY-caged compounds, <b>5</b> (VUF25657) and <b>6</b> (VUF25678), demonstrating 10-100-fold reduction in affinity for their respective receptors. Notably, the caged H<sub>3</sub>R agonist, VUF25657, exhibits approximately a 100-fold reduction in functional activity. The photo-uncaging of VUF25657 at 560 nm resulted in the release of immepip, thereby restoring binding affinity and potency in functional assays. This approach presents a promising method to achieve optical control of H<sub>3</sub>R receptor pharmacology. |
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| Item Description: | 10.3390/ph17040536 1424-8247 |