Photoswitchable Diazocine Derivative for Adenosine A Receptor Activation in Psoriasis

Overview

Journal J Am Chem Soc

Publisher American Chemical Society

Specialty Chemistry

Date 2024 Dec 16

PMID 39680577

Authors

Marc Lopez-Cano

Mirko Scortichini

Dilip K Tosh

Veronica Salmaso

Tongil Ko

Gloria Salort

Ingrid Filgaira

Concepcio Soler

Dirk Trauner

Jordi Hernando

Kenneth A Jacobson

Francisco Ciruela

Affiliations

Soon will be listed here.

Abstract

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. As a result, our photoswitchable agonist allowed the precise modulation of AR function both and , which led to a clear light-controlled pharmacotherapeutic effect on mouse skin lesions. This breakthrough not only demonstrates the potential of diazocine photoswitches for photopharmacology but also paves the way for the development of new strategies for skin-related diseases that require localized and temporally controlled drug action.

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