Exploring the kinetic selectivity of drugs targeting the β₁ -adrenoceptor.

ABSTRACT: In this study, we report the β₁ -adrenoceptor binding kinetics of several clinically relevant β_1/2 -adrenoceptor (β_1/2 AR) agonists and antagonists. [³ H]-DHA was used to label CHO-β₁ AR for binding studies. The kinetics of ligand binding was assessed using a competition association binding method. Ligand physicochemical properties, including logD_7.4 and the immobilized artificial membrane partition coefficient (K_IAM ), were assessed using column-based methods. Protein Data Bank (PDB) structures and hydrophobic and electrostatic surface maps were constructed in PyMOL. We demonstrate that the hydrophobic properties of a molecule directly affect its kinetic association rate (k_on ) and affinity for the β

SUBMITTER: Sykes DA 

PROVIDER: S-EPMC9237807 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature