Studies on the interaction of daurisoline alkaloid derivatives and calmodulin by fluorescence spectroscopy.

Abstract

A new kind of bisbenzylisoquinoline compounds, daurisoline alkaloid derivatives, has been found to be very potent calmodulin antagonists. The fluorescence spectra of interaction between these derivatives and calmodulin have been studied. The experimental results showed that these derivatives could interact with calmodulin resulting in forming a complex and diminishing fluorescence intensity. The process was Ca2(+)-dependent. These derivatives can bind to calmodulin and result in conformational change of calmodulin. But the binding site of these derivatives on calmodulin may be different from that of trifluoperazine. These derivatives can not displace all Ca2+ on calmodulin like trifluoperazine can do. Their abilities of antagonizing calmodulin to stimulate calmodulin-dependent cyclic nucleotide phosphodiesterase and the affinities of binding to calmodulin were related to hydrophobicity of substituting groups in side chain of these derivatives. Increase in hydrophobicity of these substituting groups increased binding of the derivatives and generally increased the inhibition of calmodulin stimulation of calmodulin-dependent cyclic nucleotide phosphodiesterase.