Galanthamine as bis-functional ligand for the acetylcholinesterase.
Acetylcholinesterase plays a key role in the development of Alzheimer's disease as this enzyme is responsible for cleavage of the neurotransmitter acetylcholine, and, according to recent investigations, also promotes aggregation of beta-amyloid peptides, which causes plaque formation in synaptic areas. We have performed a molecular modeling study to investigate bis-galanthamine derivatives connected by a methylene spacer of varying length as dual acting acetylcholinesterase ligands. Our results suggest that such ligands indeed can interact simultaneously with both biological functions of the enzyme and should therefore serve as the basis for a further development of bis-functional Alzheimer drugs.
University of Paderborn, FB13-Organic Chemistry, Warburger Str. 100, 33098 Paderborn, Germany.
Edgar
E
Luttmann
Elmar
E
Linnemann
Gregor
G
Fels
D000110:Acetylcholinesterase / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D005702:Galantamine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism*; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding
D008024:Ligands; D005702:Galantamine; D000110:Acetylcholinesterase