E2020 with active site and unteracts
Introduction
E2020, marketed as Aricept, is a member of a large family of N-benzylpiperidine- based acetylcholinesterase (AChE) inhibitors developed, synthesized and evaluated by the Elsai Company in Japan. These Inhibitors were designed on the basis of QSAR studies, prior to elucidation of the three-dimensional structure of Torpedo californica AChE (TCAChE). It significantly enhances performance in animal models of cholinergic hypofunction and has a high affinity for AChE. binding to both electric eel and mouse AChE in the nanomolar range.
Exploring the Structure
E2020 has a unique orientation along the active-site gorge, extending from the anionic subsite of the active site, at the bottom, to the peripheral anlonic site, at the top, via aromatic stacking interactions with conserved aromatic acid residues. E2020 does not, however, interact directly with either the catalytic triad or the 'oxyanion hole', but only indirectly via solvent molecules.
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References
- ↑ Kryger G, Silman I, Sussman JL. Structure of acetylcholinesterase complexed with E2020 (Aricept): implications for the design of new anti-Alzheimer drugs. Structure. 1999 Mar 15;7(3):297-307. PMID:10368299
Quiz
