Calmodulin discriminates between the two enantiomers of the receptor‐operated calcium channel blocker sk&f 96365: A study using 1H‐NMR and chiral HPLC

Publisher Website
Google Scholar
Abstract
1H nuclear magnetic resonance at 360 MHz shows that SK&F 96365 (1‐{β‐[3‐(p‐methoxyphenyl)‐propyloxy]‐p‐methoxyphenethyl}‐1H‐ imidazole hydrochloride), an antagonist of mammalian receptor‐operated calcium channels, interacts with the calcium‐binding regulatory protein calmodulin (CaM). This may be inferred by a number of chemical shift changes in the spectrum of the calcium‐saturated protein induced by addition of the compound. Moreover, two well‐resolved singlets corresponding to the 2‐proton of the SK&F 96365 imidazolium moiety are observed in the spectrum over a wide range of protein:compound ratios. Separation of rac SK&F 96365 into its two enantiomers by high‐performance liquid chromatography on a cellulose tris (4‐methylbenzoate) column enabled us to show that the doubling of this NMR signal in the presence of CaM is due to a propensity of the protein to distinguish between the two optical isomers of the compound.