title: Conformational structure of some beta 1-blockers, their partitioning in lipid and the role of parasubstituents.
abstract: 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.
authors.affiliation: Department of Biophysics, Panjab University, Chandigarh.
authors.forename: F S
authors.initials: FS
authors.lastname: Nandel
authors.forename: J K
authors.initials: JK
authors.lastname: Grewal
authors.forename: B
authors.initials: B
authors.lastname: Singh
mesh_terms: D058672:Adrenergic beta-2 Receptor Antagonists; D000319:Adrenergic beta-Antagonists / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry*; D008968:Molecular Conformation; D015394:Molecular Structure
chemical_list: D058672:Adrenergic beta-2 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D008055:Lipids