304669-56-5Relevant academic research and scientific papers
Noncompetitive antagonist-binding sites of rat and housefly γ-aminobutyric acid receptors display different enantiospecificities for tert-butyl(isopropyl)bicyclophosphorothionate
Ju, Xiu-Lian,Ozoe, Yoshihisa
, p. 2337 - 2341 (2007/10/03)
The enantiomers of 4-tert-butyl-3-isopropyl-2,6,7-trioxa-1-phosphabicyclo[2.2.2]octane 1-sulfide (TBIPPS) were prepared in nine steps from diethyl tert-butylmalonate, and their abilities to compete with [3H]1-(4-ethynylphenyl)-4-n-propyl-2,6,7-trioxabicyclo[2.2.2]octane (EBOB), a noncompetitive antagonist of ionotropic γ-aminobutyric acid (GABA) receptors, at their binding site were investigated using rat brain and housefly head membranes. The (S)-(-)-isomer of TBIPPS (IC50=398 nM) was more potent than was the (R)-(+)-isomer of TBIPPS (IC50=1220 nM) in rat receptors, while the potencies of (S)-TBIPPS (IC50=104 nM) and (R)-TBIPPS (IC50=94.4 nM) in housefly receptors were almost the same. The different enantiospecificities of rat and housefly receptors indicate that the three-dimensional structure of the binding site might be different between these receptors. In a region of the rat binding site there might be a steric bulk that interacts less favorably with (R)-TBIPPS than with (S)-TBIPPS, while in the corresponding region of the housefly binding site there might not be such a steric bulk that leads to specificity for these compounds. Copyright (C) 2000 Elsevier Science Ltd.
