Weerakkody Dhammika, Andreev Oleg A, Reshetnyak Yana K
Department of Physics, University of Rhode Island, Kingston, RI 02881, United States.
Biochem Biophys Rep. 2016 Dec;8:290-295. doi: 10.1016/j.bbrep.2016.10.001. Epub 2016 Oct 8.
The investigation of pH-dependent membrane-associated folding has both fundamental interest and practical applications for targeting of acidic tumors and specific delivery of therapeutic molecules across membrane of cancer cells. We and others investigated molecular mechanism and medical uses of class of water soluble membrane peptides, pH (Low) Insertion Peptides (pHLIP peptides). Here we employed optical spectroscopy methods to study interactions of the truncated pHLIP peptide (Short pHLIP) with lipid bilayer of membrane. Tryptophan fluorescence, CD and OCD data indicate on pH-triggered formation of transmembrane helical structure. Dual quenching and FRET assays demonstrated that Short pHLIP peptide spans lipid bilayer of membrane similar to Long pHLIP peptides. Truncated pHLIP peptides with multiple charged and protonatable residues in their sequences potentially can make these peptides to be less hydrophobic compared to Long pHLIP peptides, and might have utility in tumor imaging, and potentially, in pH-regulated cytoplasmic delivery of moderately hydrophobic drugs.
对pH依赖性膜相关折叠的研究对于靶向酸性肿瘤以及治疗性分子跨癌细胞膜的特异性递送而言，既具有根本的研究意义，又具有实际应用价值。我们和其他研究人员对一类水溶性膜肽，即pH（低）插入肽（pHLIP肽）的分子机制和医学用途进行了研究。在此，我们采用光谱学方法来研究截短型pHLIP肽（短pHLIP）与膜脂双层的相互作用。色氨酸荧光、圆二色性（CD）和光学相干层析成像（OCD）数据表明了pH触发的跨膜螺旋结构的形成。双淬灭和荧光共振能量转移（FRET）分析表明，短pHLIP肽跨越膜脂双层的方式与长pHLIP肽相似。其序列中带有多个带电和可质子化残基的截短型pHLIP肽，相比长pHLIP肽而言，可能会使其疏水性降低，并且可能在肿瘤成像以及潜在地在pH调节的中等疏水性药物的胞质递送中具有应用价值。
