Defining determinant molecular properties for the blockade of the apamin-sensitive SKCa channel in guinea-pig hepatocytes: the influence of polarizability and molecular geometry.
QSAR studies of a series of blockers of the SK(Ca) channel in guinea-pig hepatocytes suggests that the polarizability of the blocker is an important factor controlling the binding to the channel. It is suggested that, upon binding, an ion-pair is formed, a process that is promoted by the reorganization of the water molecules. The polarizability is not adequate to describe the potency of the most potent blockers with a good stereochemical fit to the channel, presumably due to more specific interactions taking place.
Galanakis
Dimitrios
D
Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotelian University of Thessaloniki, 541 24 Thessaloniki, Greece. dgalana@pharm.auth.gr
Ganellin
C Robin
CR
D000818:Animals; D001030:Apamin / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D006168:Guinea Pigs; D022781:Hepatocytes / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008968:Molecular Conformation; D024681:Potassium Channels, Calcium-Activated / Q000037:antagonists & inhibitors* / Q000737:chemistry*
D024681:Potassium Channels, Calcium-Activated; D001030:Apamin