In line with the docking predictions, the overall structure of the TbPTR1 complexes resembles the complex with 1b (compare Figure with 3C). In agreement with the design objective, the N-ethyl moiety of 2a was found to form van der Waals interactions with Val206 and Trp221 on the hydrophobic side of the pocket (Figure ). The bulkier N-propylhydroxyl moiety of 2e forms direct and water-mediated hydrogen bonds with Asp161 and receives an intramolecular hydrogen bond from the amine in position 4 on the pteridine system (Figure ). The structure of LmPTR1 in complex with 2e (Figure ) closely resembles that observed in TbPTR1, except for the terminal piperidine moiety (Figure ). The latter moiety is highly flexible -a possible orientation is reported in the crystal structure, but further orientations cannot be excluded.