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Differential sensitivity of pHLIP to ester and ether lipids.
Chemistry and Physics of Lipids ( IF 3.4 ) Pub Date : 2019-12-10 , DOI: 10.1016/j.chemphyslip.2019.104849
Bhagyashree D Rao 1 , Hirak Chakraborty 2 , Arunima Chaudhuri 3 , Amitabha Chattopadhyay 4
Affiliation  

pH (low) insertion peptide (pHLIP) is a polypeptide from the third transmembrane helix of bacteriorhodopsin. The pH-dependent membrane insertion of pHLIP has been conveniently exploited for translocation of cargo molecules and as a novel imaging agent in cancer biology due to low extracellular pH in cancer tissues. Although the application of pHLIP for imaging tumor and targeted drug delivery is well studied, literature on pHLIP-membrane interaction is relatively less studied. Keeping this in mind, we explored the differential interaction of pHLIP with ester and ether lipid membranes utilizing fluorescence and CD spectroscopy. We report, for the first time, higher binding affinity of pHLIP toward ether lipid relative to ester lipid membranes. There results gain relevance since Halobacterium halobium (source of bacteriorhodopsin) is enriched with ether lipids. In addition, we monitored the difference in microenvironment around pHLIP tryptophans utilizing red edge excitation shift and observed increased motional restriction of water molecules in the interfacial region in ether lipid membranes. These changes were accompanied with increase in helicity of pHLIP in ether lipid relative to ester lipid membranes. Our results assume further relevance since ether lipids are upregulated in cancer cells and have emerged as potential biomarkers of various diseases including cancer.

中文翻译:

pHLIP对酯和醚脂质的差异敏感性。

pH(低)插入肽(pHLIP)是来自细菌视紫红质的第三个跨膜螺旋的多肽。pHLIP的pH依赖性膜插入已被方便地用于货物分子的易位,并且由于癌症组织中的细胞外pH值低,在癌症生物学中作为一种新颖的成像剂。尽管已经很好地研究了pHLIP在成像肿瘤和靶向药物递送中的应用,但是关于pHLIP-膜相互作用的文献研究相对较少。牢记这一点,我们利用荧光和CD光谱研究了pHLIP与酯和醚脂质膜的微分​​相互作用。我们首次报道了pHLIP对醚脂质相对于酯脂质膜的更高的结合亲和力。由于卤化盐杆菌(细菌视紫红质的来源)富含醚类脂质,因此结果具有相关性。此外,我们利用红边激发位移监测了pHLIP色氨酸周围微环境的差异,并观察到了醚脂质膜界面区域中水分子运动受限的增加。这些变化伴随着醚脂质中pHLIP相对于酯脂质膜的螺旋度增加。由于醚脂质在癌细胞中上调,并且已成为包括癌症在内的各种疾病的潜在生物标志物,因此我们的结果具有进一步的相关性。我们利用红边激发位移监测了pHLIP色氨酸周围微环境的差异,并观察到了醚脂质膜界面区域中水分子运动受限的增加。这些变化伴随着醚脂质中pHLIP相对于酯脂质膜的螺旋度增加。由于醚脂质在癌细胞中上调,并且已成为包括癌症在内的各种疾病的潜在生物标志物,因此我们的结果具有进一步的相关性。我们利用红边激发位移监测了pHLIP色氨酸周围微环境的差异,并观察到了醚脂质膜界面区域中水分子运动受限的增加。这些变化伴随着醚脂质中pHLIP相对于酯脂质膜的螺旋度增加。由于醚脂质在癌细胞中上调,并且已成为包括癌症在内的各种疾病的潜在生物标志物,因此我们的研究结果具有进一步的相关性。
更新日期:2019-12-11
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