Bannister Mark L, Williams Alan J
Department of Cardiac Medicine, National Heart and Lung Institute, Imperial College London, Dovehouse Street, London SW3 6LY, UK.
Biochem Biophys Res Commun. 2004 Apr 30;317(2):397-400. doi: 10.1016/j.bbrc.2004.03.073.
The broad range of ligands known to modulate ryanodine receptor activity includes a class of heteroaromatic compounds displaying relatively poor efficacy. Greater understanding of the physicochemical properties that predispose these molecules to interaction with the channel should facilitate the rational design of more potent analogues. To this end we are examining the structure-activity relationship for simple heteroaromatic compounds. Efficacy is assessed by the ability to stimulate [3H]ryanodine binding to heavy sarcoplasmic reticulum vesicles. The propensity to activate the channel requires notably little chemical functionality and is associated with the capacity for charge-transfer complex formation in conjunction with steric bulk.
已知可调节兰尼碱受体活性的配体种类繁多，其中包括一类药效相对较差的杂环芳香化合物。深入了解使这些分子易于与通道相互作用的物理化学性质，应有助于更合理地设计出更有效的类似物。为此，我们正在研究简单杂环芳香化合物的构效关系。通过刺激[3H]兰尼碱与重肌浆网囊泡结合的能力来评估药效。激活通道的倾向明显不需要太多化学官能团，并且与结合空间体积形成电荷转移复合物的能力有关。
