title: Consequences of linker length alteration of the α7 nicotinic acetylcholine receptor (nAChR) agonist, SEN12333.
abstract: A series of ligands based on SEN12333, containing either contracted or elongated alkyl chains, were synthesized and evaluated in molecular docking studies against a homology model of the α7 nicotinic acetylcholine receptor (nAChR) subtype. The predicted binding of all ligands was highly similar, with the exception of the analog containing a 5 methylene unit spacer. However, in vitro competition binding assays revealed that the ligands possessed dissimilar binding affinities, with a K(i) range of more than an order of magnitude (K(i)=0.50 to >10 μM), and only SEN12333 itself exhibited functional activity at the α7 nAChR.
authors.affiliation: School of Chemistry, The University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: Corinne
authors.initials: C
authors.lastname: Beinat
authors.forename: Samuel D
authors.initials: SD
authors.lastname: Banister
authors.forename: Saundra
authors.initials: S
authors.lastname: van Prehn
authors.forename: Munikumar Reddy
authors.initials: MR
authors.lastname: Doddareddy
authors.forename: David
authors.initials: D
authors.lastname: Hibbs
authors.forename: Michael
authors.initials: M
authors.lastname: Sako
authors.forename: Mary
authors.initials: M
authors.lastname: Chebib
authors.forename: Thao
authors.initials: T
authors.lastname: Tran
authors.forename: Nour
authors.initials: N
authors.lastname: Al-Muhtasib
authors.forename: Yingxian
authors.initials: Y
authors.lastname: Xiao
authors.forename: Michael
authors.initials: M
authors.lastname: Kassiou
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D006801:Humans; D007700:Kinetics; D008024:Ligands; D008958:Models, Molecular; D009025:Morpholines / Q000138:chemical synthesis* / Q000378:metabolism; D018722:Nicotinic Agonists / Q000138:chemical synthesis* / Q000378:metabolism; D011485:Protein Binding; D011725:Pyridines / Q000138:chemical synthesis* / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000378:metabolism; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: C540749:5-morpholin-4-ylpentanoic acid (4-pyridin-3-ylphenyl)amide; C579167:Chrna7 protein, human; D008024:Ligands; D009025:Morpholines; D018722:Nicotinic Agonists; D011725:Pyridines; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor