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. Author manuscript; available in PMC: 2017 Jan 15.
Published in final edited form as: ACS Chem Biol. 2015 Nov 6;11(1):121–131. doi: 10.1021/acschembio.5b00847

Figure 7.

Figure 7

A bivalent inhibitor of ERK2. (A) (Top panel) SNAPtag-DARPin fusion that was generated for this study. The exact sequence for this construct is shown in SI, Figure S11. (Bottom panel) The binding sites for the ligands of the bivalent inhibitor are superimposed on a crystal structure of ERK2, PDB ID 3ZUV. (B) In vitro activities of 4, SNAPtag proteins and assembled SNAPtag-4 conjugates against doubly phosphorylated ERK2. Values shown are the average of assays performed in triplicate ± SEM. ‡ indicates that only partial inhibition of ERK2 was observed (see plot below). (C) In vitro activity of 4 and assembled SNAPtag-4 construct against activated ERK2, JNK2, and p38α. IC50 values are shown as ratios and plotted on a log10-based scale. A blue dashed line denotes an IC50 ratio of one, indicating equipotent inhibition of ERK2 and either JNK2 or p38α. (D) RB50 curves of the phosphorylated and nonphosphorylated ERK activation-loop peptide for SNAP(pE59)-4. Curves are shown in pink for the phosphorylated peptide and blue for the nonphosphorylated peptide.