Istituto di Cristallografia, Consiglio Nazionale delle Ricerche, Area della Ricerca di Roma, P.O. Box 10, I-00016 Monterotondo Stazione(Roma), Italy.
J Med Chem. 2010 Jan 28;53(2):745-51. doi: 10.1021/jm901296p.
N-Piperidinopropyl-galanthamine (2) and N-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).
N-哌啶丙基-石蒜碱（2）和 N-蔗糖己基-石蒜碱（3）被用于研究加利福尼亚海兔乙酰胆碱酯酶（TcAChE）活性位点峡谷沿线的相互作用位点。2.3 A 解析的 TcAChE-2 晶体结构表明，2 中的 N-哌啶丙基基团不是沿着峡谷伸展，而是折叠在石蒜碱部分上。这一结果出人意料，因为这三个碳烷基链的长度刚好足以使庞大的哌啶基团放置在峡谷中间瓶颈处（Tyr121、Phe330）的上方。2.2 A 的 TcAChE-3 晶体结构证实，与峡谷底部和入口处的双重相互作用增强了抑制活性：在这类衍生物中，具有六个碳原子的链具有与外周阴离子位点（PAS）进行最佳相互作用的正确长度。
