ANTI-MITOGENIC BOMBESIN ANTAGONISTS

荧光技术将被用来检测分子 平滑肌肌球蛋白功能的调节机制。 将使用荧光和/或发色化合物来标记 肌球蛋白活性部位，两种不同类型的轻链，以及 分子杆状部分上的特定位置。上面的这些标签 肌球蛋白将被用来探测构象转变 可能在平滑肌调节机制中起重要作用 通过轻链磷酸化。这些探头之间的距离 和其他在肌动蛋白特定地点的记者小组将 通过荧光能量转移技术测量。这个 调节轻链的磷酸化作用 肌球蛋白轻链激酶或蛋白激酶C在这些距离上 将会被检查。这些探头也将用于实验 设计用于评估极性、大小、形状和灵活性 肌球蛋白分子在条件下的6个S(延长)到10个 已知存在S(折叠)形式的肌球蛋白。使用这些 方法，假设的头部和尾部的连接点 肌球蛋白分子在调节机制中起着关键作用 将对肌球蛋白进行测试。这一信息将是 有助于确定磷酸化如何依赖于 体外观察到的构象变化与生理上的 体内肌球蛋白细丝内的重要结构变化。

Fluorescence techniques will be used to examine the molecular mechanism of regulation of smooth muscle myosin function. Fluorescent and/or chromophoric compounds will be used to label the myosin active site, the two different kinds of light chains, and a specific site on the rod portion of the molecule. These labels on myosin will be used to probe conformational transitions which may be important to the mechanism of smooth muscle regulation by light chain phosphorylation. Distances between these probes and other reporter groups at specific sites on actin will be measured by fluorescence energy transfer techniques. The effects of phosphorylation of the regulatory light chains by either myosin light chain kinase or protein kinase C upon these distances will be examined. These probes will also be used in experiments designed to assess the polarity, size, shape and flexibility of the myosin molecules under conditions where the 6 S (extended) to 10 S (folded) forms of myosin are known to exist. Using these approaches, the hypothesis that the head-tail junction of the myosin molecule plays a key role in the mechanism of regulation of smooth muscle myosin will be tested. This information will be useful to determine how the phosphorylation dependent conformational changes observed in vitro relate to physiologically important structural changes within myosin filaments in vivo.