Saludes Jonel P, Morton Leslie A, Ghosh Nilanjan, Beninson Lida A, Chapman Edwin R, Fleshner Monika, Yin Hang
Department of Chemistry and Biochemistry and BioFrontiers Institute, University of Colorado Boulder, Boulder, Colorado 80309, United States.
ACS Chem Biol. 2012 Oct 19;7(10):1629-35. doi: 10.1021/cb3002705. Epub 2012 Jul 17.
The generation of highly curved membranes is essential to cell growth, division, and movement. Recent research in the field is focused to answer questions related to the consequences of changes in the topology of the membrane once it is created, broadly termed as membrane curvature sensing. Most probes that are used to study curvature sensing are intact membrane active proteins such as DP1/Yop1p, ArfGAP1, BAR domains, and Synaptotagmin-I (Syt1). Taking a cue from nature, we created the cyclic peptide C2BL3C based on the membrane penetration C2B loop 3 of Syt1 via "Click" chemistry. Using a combination of spectroscopic techniques, we investigated the peptide-lipid interactions of this peptide with synthetic phospholipid vesicles and exosomes from rat blood plasma. We found that the macrocycle peptide probe was selective for lipid vesicles with highly curved surfaces (d < 100 nm). These results suggested that C2BL3C functions as a selective detector of highly curved phospholipid bilayers.
高度弯曲膜的生成对于细胞生长、分裂和运动至关重要。该领域的最新研究集中于回答与膜拓扑结构改变（一旦形成，广义上称为膜曲率传感）的后果相关的问题。大多数用于研究曲率传感的探针是完整的膜活性蛋白，如DP1/Yop1p、ArfGAP1、BAR结构域和突触结合蛋白-I（Syt1）。从自然界获得灵感，我们通过“点击”化学基于Syt1的膜穿透C2B环3创建了环肽C2BL3C。使用多种光谱技术的组合，我们研究了该肽与合成磷脂囊泡和大鼠血浆来源外泌体的肽-脂质相互作用。我们发现大环肽探针对于具有高度弯曲表面（d < 100 nm）的脂质囊泡具有选择性。这些结果表明C2BL3C可作为高度弯曲磷脂双层的选择性检测器。
