This complete study - from rational design to validation by X-ray crystallography allowed us to discover two sub-nanomolar hAChE inhibitors (430 and 530 pM) grafted with an easily derivatized linker directed toward the AChE peripheral site. The crystal structure of mouse AChE in complex with compound 4 was solved and confirms the favorable position of the triazole in the active site gorge, paving the way for a new class of bifunctional ligands.
Representative scheme of ACHE structure and an image from PDBsum server
Databases
PDB-Sum
4A16 Previously Class, Architecture, Topology and Homologous superfamily - PDB-Sum server
FSSP
4A16Fold classification based on Structure-Structure alignment of Proteins - FSSP server
