1. Conformation-locking antibodies for the discovery and characterization of KRAS inhibitors
- Author
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Christopher W. Davies, Angela J. Oh, Rana Mroue, Micah Steffek, John M. Bruning, Yang Xiao, Siyu Feng, Sangeeta Jayakar, Emily Chan, Vidhyalakshmi Arumugam, Sean Carlo Uribe, Jake Drummond, Alexandra Frommlet, Cheng Lu, Yvonne Franke, Mark Merchant, Hartmut Koeppen, John G. Quinn, Sushant Malhotra, Steve Do, Lewis Gazzard, Hans E. Purkey, Joachim Rudolph, Melinda M. Mulvihill, James T. Koerber, Weiru Wang, and Marie Evangelista
- Subjects
Proto-Oncogene Proteins p21(ras) ,Neoplasms ,Mutation ,Biomedical Engineering ,Humans ,Molecular Medicine ,Bioengineering ,Ligands ,Applied Microbiology and Biotechnology ,Antibodies ,Biotechnology - Abstract
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 KRAS, we discovered CLAMPs that recognize the open conformation of KRAS
- Published
- 2022
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