Beta ₂ - Adrenergic Receptor Chromatography For Research On Relationship Between Structural Parameters Of Drug Binding Constant -

Active components selecting of drugs in the complex system is a hot topic studied at Pharmaceutical Research, searching and discovering lead compounds with biological activity is a crucial aspect. In recent years, drug screening models that use receptor as a target have made great progress,β2-adrenergic receptor (β2-AR) Chosen in this paper is receptor in the surface of cell wall, Participating in many physiological and pathological process of body, and it is the primary target when asthma drugs effect on the body. We used the characteristic that receptor and ligand binding together Specifically, by researching the seven specific binding tool drugs, found the relationship between binding constant and molecular structure parameters, finally got the relationship of reserved-structure so as to provide guidance for Selecting and designing of drug molecules.There are three chapters in this paper, The author's main contributions are as follows:1. Based on existent methods of Separatingβ2-AR, using bacterial culture and affinity chromatography, we obtained high-purityβ2-AR that the experimental needed, and then immobilized receptors on the surface of macro porous silica gel by chemical coupling method, finally got theβ2-AR chromatography column. Using tool drugs such as methoxyphenamine, salbutamol, botero inspect the bioactivity of the column,the result show that after the purified receptor bonded to the silica surface, it still retained biologically activity, and can be specifically combined with the tool drugs, herefore can be used for researching relationship between drug binding constants and structural parameters.2. Based on the established model of receptor chromatography, we determined the association constant and the number of binding sites of tool drugs with the methods of frontal analysis.The result show that the association constants of salbutamo, clorprenaline, Methoxyphenamine, botero, formoterol, clenbuterol, bambuterol are 15.61×105M-1,2.52×105M-1,2.33×105M-1,3.35×105M-1,18.87×105 M-1,2.74×105M-1 and 10.57×105 M-1.3.We got the structural parameters by insepcting the literature, and then can obtain the relationship between binding constant and structural parameters, finally we found that the structure parameters such as logP, hydrogen bond number (Ha), molar refractionand and dipole moment have a certain correlation with binding constants, which were negatively correlated with the logP, the linear equation was Ka=16982-5828logP; which were positively correlated with the number of hydrogen bonds, the linear equation was Ka=-3488+1297Ha, and the number of hydrogen bonds had more influence than logP.