Nandel F S, Grewal J K, Singh B
Department of Biophysics, Panjab University, Chandigarh.
Indian J Biochem Biophys. 1995 Aug;32(4):207-12.
The conformational structure of beta1-blockers metoprolol, atenolol and practolol has been investigated by PCILO method. The aminoalkanol moiety adopts the same conformation in all these compounds. These beta-antagonists differ only in the conformation adopted by the substituent para to the aminoalkanol moiety. The graphical representation of the B1-antagonists for the final conformation reveals that only in the S-form, three interacting sites, namely, aromatic moiety, the beta-hydroxyl group and the -NH2(+) groups of aminoalkanol moiety are available for interactions with the receptor. The interaction of the aryloxy oxygen of the beta-antagonists with water molecule has also been taken into account. A linear relationship was obtained between log K (the partitioning of the beta-blocker in DMPC and also in octanol/water) and the potencies of these beta1-antagonists. Possibly, the role of para substituent is to act as an anchor by partitioning in the lipid bilayer so that the beta1-antagonist adopts the proper orientation for binding to the receptor.
已通过PCILO方法研究了β1受体阻滞剂美托洛尔、阿替洛尔和普拉洛尔的构象结构。在所有这些化合物中，氨基链烷醇部分采取相同的构象。这些β受体拮抗剂仅在氨基链烷醇部分对位取代基所采取的构象上有所不同。β1受体拮抗剂最终构象的图形表示显示，仅在S型中，三个相互作用位点，即芳香部分、β-羟基和氨基链烷醇部分的-NH2(+)基团可用于与受体相互作用。还考虑了β受体拮抗剂的芳氧基氧与水分子的相互作用。在log K（β受体阻滞剂在二肉豆蔻酰磷脂酰胆碱以及辛醇/水中的分配）与这些β1受体拮抗剂的效力之间获得了线性关系。对位取代基的作用可能是通过在脂质双层中分配而充当锚定物，从而使β1受体拮抗剂采取与受体结合的适当取向。
