To test the feasibility of our proposed strategy, we first confirmed that treating biotinylated proteinbound beads with guanidine chloride (up to 8 M) did not disrupt the interaction between biotin and streptavidin (Supplementary Figure ). Subsequently, we used a model mRNA template encoding a previously identified non-covalent peptide ligand (3.1B) of the first bromodomain of BRD3, BRD3-BD1, to confirm the effectiveness of our denaturing washes in removing non-covalent ligands.