Binding Affinity of Candesartan, Losartan, Telmisartan and Valsartan with Angiotensin II Receptor 1 Subtype
Keywords:Binding affinity, AT1 antagonists, radioligand binding, binding sites
This study was designed to examine the interaction in the binding of selective angiotensin II receptor antagonists towards angiotensin II type 1 receptor. The AT1 antagonists used in this study were valsartan, candesartan and losartan. Wild type AT1 receptors were transiently expressed in COS-7 cells and the expressed protein was isolated. The binding affinities of agonist and these four AT1 antagonists were determined towards AT1 receptors with the help of radioligand binding studies. The binding affinity of candesartan has been found to be maximum having a pKi value of 8.61±0.21 whereas losartan showed lowest binding affinity among the antagonists (pKi=7.17±0.07). Telmisartan also showed high (pKi=8.19±0.04) and valsartan had moderate binding affinity (pKi=7.65±0.12) towards AT1 receptors. The results of the study suggested that candesartan interacts very strongly with the receptor which is consistent with the maximum number of binding sites of in the chemical structure of candesartan. On the other hand, losartan has lower number of binding sites with the amino acid residues of AT1 receptor and as a result it showed the minimum affinity towards the receptor.
Bangladesh Pharmaceutical Journal 16(1): 10-14, 2013