Figure 3.
Optimizing RNF4 covalent ligands using gel-based ABPP. (A) Derivatives of TRH 1–23 were tested against IA-rhodamine labeling of RNF4 using gel-based ABPP. Silver stained gels are also shown to visualize total protein content. (B) CCW16 was tested against IA-rhodamine labeling of RNF4 using gel-based ABPP. For parts A and B, covalent ligands were preincubated with pure RNF4 protein for 30 min prior to IA-rhodamine labeling for 1 h. Proteins were subjected to SDS/PAGE and visualized by in-gel fluorescence. In part B, gels were quantified by densitometry to calculate IC50 values. The gel shown in part B is a representative gel from n = 3. (C) Covalent docking of CCW 16 bound to either C132 or C135 in RNF4.