{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T18:24:35Z","timestamp":1789064675450,"version":"build-2803163510"},"reference-count":42,"publisher":"Wiley","issue":"41","license":[{"start":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T00:00:00Z","timestamp":1725494400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T00:00:00Z","timestamp":1725494400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Angew Chem Int Ed"],"published-print":{"date-parts":[[2024,10,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>We showcase the successful combination of photochemistry and kinetic target\u2010guided synthesis (KTGS) for rapidly pinpointing enzyme inhibitors. KTGS is a fragment\u2010based drug discovery (FBDD) methodology in which the biological target (BT) orchestrates the construction of its own ligand from fragments featuring complementary reactive functionalities. Notably, fragments interacting with the protein binding sites leverage their spatial proximity, facilitating a preferential reaction. Consequently, the resulting bivalent ligand exhibits heightened affinity. Within the realm of KTGS strategies, in situ click chemistry stands out as the most widely used to identify potent protein binders. This approach requires significant protein contributions, such as binding interactions and appropriate orientations of fragments, to overcome high activation barriers. This leads to prolonged incubation times and the potential for generating false negatives, thereby limiting this strategy to proteins that are stable enough in buffer. We herein unveil the possibility to integrate photochemistry into the realm of KTGS, accelerating the ligation reaction between fragments to a time scale of minutes. This approach should significantly expand the narrow reactivity window of traditional KTGS reactions, paving the way for the exploration and development of novel photo\u2010KTGS reactions.<\/jats:p>","DOI":"10.1002\/anie.202407888","type":"journal-article","created":{"date-parts":[[2024,7,14]],"date-time":"2024-07-14T10:10:25Z","timestamp":1720951825000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Light\u2010Induced Unlocking Reactivity of Fragments for Fast Target\u2010Guided Synthesis of Carbonic Anhydrase Inhibitors"],"prefix":"10.1002","volume":"63","author":[{"given":"Chlo\u00e9","family":"Puteaux","sequence":"first","affiliation":[{"name":"Normandie, Univ Rouen Normandie, INSA Rouen, CNRS, Normandie Univ COBRA UMR 6014, INC3MFR 3038  F-76000 Rouen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Toubia","sequence":"additional","affiliation":[{"name":"Normandie, 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