Figure 1.

Structure-based design of AP22408. (A) X-ray crystal structure of citrate complexed to the pTyr-binding pocket of Src SH2 depicting hydrogen bonding atoms. (B) Model of Dpp in the pTyr binding pocket of Src SH2, highlighting the hydrogen bonding network. (C) Model of 3 complexed with Lck SH2, illustrating the solvent accessible surface detailed in terms of both hydrophobic and hydrogen bonding interactions. Yellow colors indicate hydrophobic surfaces, blue colors indicate hydrogen bond accepting surfaces, and red colors indicate hydrogen bond donating surfaces. (D) Model of AP22408 in Lck SH2 highlighting the hydrophobic interactions of the bicyclic template.