申请人:The Regents of the University of California
公开号:US11187660B2
公开(公告)日:2021-11-30
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, coumarins, cyanines, bimanes, and difuloroboradizaindacenes, 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符合式的结构:E-M-A,其中 A 是荧光团,选自香蒽类、香豆素类、氰胺类、双烷类和二氟硼二氮杂环丁烯类,在生理 pH 值下带电;M 是分子线;E 是疏水基,其中 A 和 E 能够参与光诱导的分子内电子转移,在电压条件下淬灭 A 的荧光。使用时,本发明的化合物具有膜渗透性,并在细胞膜内定向,使带电分子位于脂质双分子层的外侧小叶,疏水分子和分子线与脂质双分子层的疏水部分结合。电子转移率、荧光强度和淬灭都会随着跨膜电位的变化而改变。