Caged Monomethyl Auristatin F (MMAF) for Cell-Specific Activation Using a 488-nm-Optimized Photolabile Group

Article Article scientifique Article Caged Monomethyl Auristatin F (MMAF) for Cell-Specific Activation Using a 488-nm-Optimized Photolabile Group eng 2026-06-03 author Lai Yuhang 406250 Chimie organique (groupe 5) (CHOR5) author Russo Francesco 956582 Chimie organique (groupe 5) (CHOR5) author Fuerstenberg Alexandre 0000-0002-6227-3122 135518 Département de chimie minérale et analytique (CHIAM) author Winssinger Nicolas 0000-0003-1636-7766 769664 Département de chimie organique (CHIOR) 10.1021/jacsau.6c00203 2691-3704 https://pubs.acs.org/doi/10.1021/jacsau.6c00203 Photolabile protecting groups (PPGs) are central tools for achieving precise spatial and temporal control of bioactive molecules in living systems. Their practical utility is critically dependent on efficient uncaging under biologically compatible conditions. Here, we report a coumarin-based PPG specifically optimized for 488 nm excitation, a ubiquitous laser line in fluorescence microscopy, enabling uncaging under irradiation conditions comparable to those used for GFP imaging. We applied the optimized PPG to cage the C-terminal carboxylate of monomethyl auristatin F (cMMAF), converting a membrane-impermeant antimitotic agent into a cell-permeant prodrug that regenerates an impermeant MMAF upon photoactivation. We showcase its utility through the light-triggered release of MMAF using irradiance typically used for imaging. We demonstrate the ability to confine the pharmacological activity of MMAF to a single cell, sparing adjacent cells (neighboring effect). Dewey 540 Swiss National Science Foundation Encoding and programing chemical biocircuitry 219316 CH 40 Département de chimie minérale, analytique et appliquée 145 36 Département de chimie organique 141 false 762 Groupe Winssinger JACS Au d07fbc76-220d-4f5f-af7b-ec4eac900548 Article (Published version) Public 210x-CagedMMAF.pdf 8518327 application/pdf CC BY-4.0 75989d97c6cde7573b26869ddc470e0df57fe80b780c4bc8a33830bafb7e509b Vignette Public TOC.png 163197 image/png openAccess Faculté des sciences / Section de chimie et biochimie / Département de chimie minérale, analytique et appliquée Faculté des sciences / Section de chimie et biochimie / Département de chimie organique

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Caged Monomethyl Auristatin F (MMAF) for Cell-Specific Activation Using a 488-nm-Optimized Photolabile Group	JACS Au			2026	10	7

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Lai, Yuhang