申请人:Miller Evan Walker
公开号:US20140093907A1
公开(公告)日:2014-04-03
Compounds and methods for determining transmembrane potential, monitoring changes in transmembrane potential, and/or drug screening are provided. In one aspect, compounds of the invention have a structure according to the formula: E-M-A, wherein A is a fluorophore, selected from xanthenes, eoumarins, cyanines, bimanes, and difluoroboradizaindacenes, charged at physiological pH; M is a molecular wire; and E is a hydrophobic moiety, wherein A and E are capable of being involved in a photo-induced, intramolecular electron transfer that quenches the fluorescence of A in response to a voltage condition. When in use, compounds of the invention are membrane-impermeant and oriented within the cell membrane such that the charged moiety localizes at the outer leaflet of the lipid bilayer and the hydrophobic moiety and molecular wire associate with the hydrophobic portion of the lipid bilayer. The rate of electron transfer, fluorescence intensity, and quenching are altered in response to changes in transmembrane potential.
本发明提供了用于确定跨膜电位、监测跨膜电位变化和/或药物筛选的化合物和方法。在一个方面,本发明的化合物具有以下结构公式:E-M-A,其中A是在生理pH下带电的荧光分子,选择自黄色素、香豆素、青菁、双咪唑和二氟硼二氮杂萘烯;M是分子导线;E是疏水基团,其中A和E能够参与光诱导的分子内电子转移,在电压条件下熄灭A的荧光。在使用时,本发明的化合物是膜不透性的,并定向于细胞膜内,使带电部分定位于脂双层的外层膜,而疏水基团和分子导线则与脂双层的疏水部分结合。在跨膜电位发生变化时,电子转移速率、荧光强度和熄灭程度会发生改变。