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C. Bartolucci, L. Haller, U. Jordis, G. Fels, D. Lamba:
"Probing Torpedo californica Acetylcholinesterase Catalytic Gorge with Two Novel Bis-functional Galanthamine Derivatives";
Journal of Medicinal Chemistry, 53 (2010), 745 - 751.

N-Piperidinopropyl-galanthamine (2) andN-saccharinohexyl-galanthamine (3) were used to investigate
interaction sites along the active site gorge of Torpedo californica actylcholinesterase (TcAChE). The
crystal structure of TcAChE-2 solved at 2.3 A ° showed that the N-piperidinopropyl group in 2 is not
stretched along the gorge but is folded over the galanthamine moiety. This result was unexpected
because the three carbon alkyl chain is just long enough for the bulky piperidine group to be placed
above the bottleneck (Tyr121, Phe330) midway down the gorge. The crystal structure of TcAChE-3 at
2.2 A ° confirmed that a dual interaction with the sites at the bottom, and at the entrance of the gorge,
enhances inhibitory activity: a chain of six carbon atoms has, in this class of derivatives, the correct
length for optimal interactions with the peripheral anionic site (PAS).

http://dx.doi.org/10.1021/jm901296p