Department of Chemistry, Merkert Chemistry Center, Boston College, 2609 Beacon Street, Chestnut Hill, Massachuetts 02467, USA.
Nat Commun. 2015 Mar 12;6:6561. doi: 10.1038/ncomms7561.
Synthetic molecules that target specific lipids serve as powerful tools for understanding membrane biology and may also enable new applications in biotechnology and medicine. For example, selective recognition of bacterial lipids may give rise to novel antibiotics, as well as diagnostic methods for bacterial infection. Currently known lipid-binding molecules primarily rely on noncovalent interactions to achieve lipid selectivity. Here we show that targeted recognition of lipids can be realized by selectively modifying the lipid of interest via covalent bond formation. Specifically, we report an unnatural amino acid that preferentially labels amine-presenting lipids via iminoboronate formation under physiological conditions. By targeting phosphatidylethanolamine and lysylphosphatidylglycerol, the two lipids enriched on bacterial cell surfaces, the iminoboronate chemistry allows potent labelling of Gram-positive bacteria even in the presence of 10% serum, while bypassing mammalian cells and Gram-negative bacteria. The covalent strategy for lipid recognition should be extendable to other important membrane lipids.
靶向特定脂质的合成分子可作为研究膜生物学的有力工具，并且可能在生物技术和医学领域开辟新的应用。例如，对细菌脂质的选择性识别可能会产生新型抗生素，以及用于细菌感染的诊断方法。目前已知的脂质结合分子主要依赖于非共价相互作用来实现脂质选择性。在这里，我们通过通过共价键形成选择性修饰感兴趣的脂质来证明可以实现靶向脂质识别。具体来说，我们报告了一种非天然氨基酸，该氨基酸在生理条件下通过亚氨基硼酸酯形成优先标记带有胺的脂质。通过靶向磷脂酰乙醇胺和赖氨酸磷酸甘油酯，这两种在细菌表面富集的脂质，亚氨基硼酸酯化学允许即使在存在 10％血清的情况下也能有效标记革兰氏阳性菌，而避开哺乳动物细胞和革兰氏阴性菌。用于脂质识别的共价策略应该可以扩展到其他重要的膜脂质。
