Sun Y, Hu Z Y, Xu L M
Division of Biochemistry, China Pharmaceutical University, Najing, Jiangsu.
Second Messengers Phosphoproteins. 1990;13(1):51-7.
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.
一种新型双苄基异喹啉化合物，即蝙蝠葛苏林碱生物碱衍生物，已被发现是非常有效的钙调蛋白拮抗剂。对这些衍生物与钙调蛋白之间相互作用的荧光光谱进行了研究。实验结果表明，这些衍生物可与钙调蛋白相互作用，形成复合物并降低荧光强度。该过程依赖于Ca2+。这些衍生物能与钙调蛋白结合并导致钙调蛋白构象改变。但这些衍生物在钙调蛋白上的结合位点可能与三氟拉嗪的不同。这些衍生物不能像三氟拉嗪那样取代钙调蛋白上所有的Ca2+。它们拮抗钙调蛋白以刺激钙调蛋白依赖性环核苷酸磷酸二酯酶的能力以及与钙调蛋白结合的亲和力与这些衍生物侧链取代基的疏水性有关。这些取代基疏水性的增加会增强衍生物的结合，并通常会增强对钙调蛋白刺激钙调蛋白依赖性环核苷酸磷酸二酯酶的抑制作用。
