Article
Conformation-locking antibodies for the discovery and characterization of KRAS inhibitors.
Nature biotechnology - 1 May 2022
Davies Christopher W, Oh Angela J, Mroue Rana, Steffek Micah, Bruning John M, Xiao Yang, Feng Siyu, Jayakar Sangeeta, Chan Emily, Arumugam Vidhyalakshmi, Uribe Sean Carlo, Drummond Jake, Frommlet Alexandra, Lu Cheng, Franke Yvonne, Merchant Mark, Koeppen Hartmut, Quinn John G, Malhotra Sushant, Do Steve, Gazzard Lewis, Purkey Hans E, Rudolph Joachim, Mulvihill Melinda M, Koerber James T, Wang Weiru, Evangelista Marie
Abstract excerpt
Small molecules that stabilize inactive protein conformations are an underutilized strategy for drugging dynamic or otherwise intractable proteins. To facilitate the discovery and characterization of such inhibitors, we created a screening platform to identify conformation-locking antibodies for molecular probes (CLAMPs) that distinguish and induce rare protein conformational states. Applying the approach to...
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