Back to Search Start Over

Consequences of linker length alteration of the α7 nicotinic acetylcholine receptor (nAChR) agonist, SEN12333.

Consequences of linker length alteration of the α7 nicotinic acetylcholine receptor (nAChR) agonist, SEN12333.

Authors :
Beinat C
Banister SD
van Prehn S
Doddareddy MR
Hibbs D
Sako M
Chebib M
Tran T
Al-Muhtasib N
Xiao Y
Kassiou M
Source :
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2012 Apr 01; Vol. 22 (7), pp. 2380-4. Date of Electronic Publication: 2012 Feb 24.
Publication Year :
2012

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.<br /> (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Details

Language :
English
ISSN :
1464-3405
Volume :
22
Issue :
7
Database :
MEDLINE
Journal :
Bioorganic & medicinal chemistry letters
Publication Type :
Academic Journal
Accession number :
22410083
Full Text :
https://doi.org/10.1016/j.bmcl.2012.02.052