Photoactivatable drugs and peptides can drive quantitative studies into receptor signaling with high spatiotemporal precision, yet few are compatible with behavioral studies in mammals. We developed CNV-Y-DAMGO-a caged derivative of the mu opioid receptor-selective peptide agonist DAMGO. Photoactivation in the mouse ventral tegmental area produced an opioid-dependent increase in locomotion within seconds of illumination. These results demonstrate the power of in vivo photopharmacology for dynamic studies into animal behavior.
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http://dx.doi.org/10.1038/s41592-023-01819-w | DOI Listing |
J Am Chem Soc
December 2024
Pharmacology Unit, Department of Pathology and Experimental Therapeutics, Faculty of Medicine and Health Sciences, Institute of Neurosciences, University of Barcelona, L'Hospitalet de Llobregat 08907, Spain.
Incorporating photoisomerizable moieties within drugs offers the possibility of rapid and reversible light-dependent switching between active and inactive configurations. Here, we developed a photoswitchable adenosine A receptor (AR) agonist that confers optical control on this G protein-coupled receptor through noninvasive topical skin irradiation in an animal model of psoriasis. This was achieved by covalently bonding an adenosine-5'-methyluronamide moiety to a diazocine photochrome, whose singular photoswitching properties facilitated repeated interconversion between a thermally stable, biologically inactive agonist form and a photoinduced, pharmacologically active configuration.
View Article and Find Full Text PDFEur J Nucl Med Mol Imaging
November 2024
Department of Medical Microbiology and Infection Prevention, University of Groningen, University Medical Center Groningen, Hanzeplein 1, Groningen, 9713GZ, The Netherlands.
Introduction: Bacterial infections pose major challenges in medicine. To guide effective infection treatment, faster and more accurate diagnostic modalities are needed. Bacteria-targeted molecular imaging can meet these needs.
View Article and Find Full Text PDFBr J Pharmacol
November 2024
Institute of Neural and Sensory Physiology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Angew Chem Int Ed Engl
November 2024
Department of Chemistry, University of Crete, Voutes, 70013 Heraklion, Greece.
Small molecule modulators are powerful tools for selectively probing and manipulating proteins in native biological systems. However, the development of versatile modulators that exhibit desired properties is hindered by the lack of a rapid and robust synthetic strategy. Here, we develop a facile and reliable one-step methodology for the generation of multifunctional toolboxes encompassing a wide variety of chemical modulators with different desired features.
View Article and Find Full Text PDFJ Am Chem Soc
October 2024
Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute for Science and Technology, Barcelona 08028, Spain.
Gamma aminobutyric acid type A receptors (GABARs) play a key role in the mammalian central nervous system (CNS) as drivers of neuroinhibitory circuits, which are commonly targeted for therapeutic purposes with potentiator drugs. However, due to their widespread expression and strong inhibitory action, systemic pharmaceutical potentiation of GABARs inevitably causes adverse effects regardless of the drug selectivity. Therefore, therapeutic guidelines must often limit or exclude clinically available GABAR potentiators, despite their high efficacy, good biodistribution, and favorable molecular properties.
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