Most amine or amide-based linkers in the constructed library were N-substituted (Fig. , SI). If the 3,4-dichlorophenyl moiety of the designed compounds bound in subpocket C (Fig. ), which we aimed to prioritize, the N-substituent would be positioned in subpocket D (Fig. ). Due to the hydrophobicity and partial solvent exposure of subpocket D, the Nsubstituents tested in silico were largely hydrophobic and some additionally had a hydrophilic moiety.