Figure 4: A covalent probe targeting the compound binding site in IL-17A.
From: Binding site elucidation and structure guided design of macrocyclic IL-17A antagonists
(A) Structure of compound 4, an analog of compound 1 designed as a covalent probe of the IL-17A binding site with a FRET IC50 of 0.2 μM. (B) Compound 4 specifically and covalently labeled full length IL-17A. IL-17A labeled by compound 4 was biotinylated by click chemistry, and pulled down by streptavidin. Eluates were immunoblotted. (C) In this model of compound 4 in the IL-17A binding pocket, the reactive sulfonyl fluoride is close to Tyr85. (D) Mass spectra of IL-17A (a) before and (b) after treatment with compound 4. The predicted mass shift resulting from a single modification of the protein was 795.3 Da.
