Robert A D'Ippolito, Dana Rabara, Maria Abreu Blanco, Emily Alberico, Matthew R Drew, Nitya Ramakrishnan, Dara Sontan, Stephanie R T Widmeyer, Grace M Scheidemantle, Simon Messing, David Turner, Michelle Arkin, Anna E Maciag, Andrew G Stephen, Dominic Esposito, Frank McCormick, Dwight V Nissley, Caroline J DeHart
Development of new targeted inhibitors for oncogenic KRAS mutants may benefit from insight into how a given mutation influences the accessibility of protein residues and how compounds interact with mutant or wild-type KRAS proteins. Targeted proteomic analysis, a key validation step in the KRAS inhibitor development process, typically involves both intact mass- and peptide-based methods to confirm compound localization or quantify binding. However, these methods may not always provide a clear picture of the compound binding affinity for KRAS, how specific the compound is to the target KRAS residue, and how experimental conditions may impact these factors...
March 18, 2024: Analytical Chemistry