Document Detail

Probing Torpedo californica acetylcholinesterase catalytic gorge with two novel bis-functional galanthamine derivatives.
MedLine Citation:
PMID:  20025280     Owner:  NLM     Status:  MEDLINE    
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).
Cecilia Bartolucci; Lars A Haller; Ulrich Jordis; Gregor Fels; Doriano Lamba
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  53     ISSN:  1520-4804     ISO Abbreviation:  J. Med. Chem.     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2010-01-21     Completed Date:  2010-03-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  745-51     Citation Subset:  IM    
Istituto di Cristallografia, Consiglio Nazionale delle Ricerche, Area della Ricerca di Roma, P.O. Box 10, I-00016 Monterotondo Stazione(Roma), Italy.
Data Bank Information
Bank Name/Acc. No.:
PDB/3I6M;  3I6Z
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MeSH Terms
Acetylcholinesterase / chemistry*
Catalytic Domain*
Crystallography, X-Ray
Galantamine / chemistry*
Molecular Probes / chemistry*
Piperidines / chemistry
Protein Binding
Structure-Activity Relationship
Reg. No./Substance:
0/Molecular Probes; 0/Piperidines; 357-70-0/Galantamine; EC

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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