Brain-transportable dipeptides across the blood-brain barrier in mice
Brain-transportable dipeptides across the blood-brain barrier in mice
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DOI：
10.1038/s41598-019-42099-9
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发表时间：
2019-04-08
影响因子：
4.6
通讯作者：
Matsui, Toshiro
中科院分区：
文献类型：
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作者：
Tanaka, Mitsuru;Dohgu, Shinya;Matsui, Toshiro
除了大脑所需的营养物质外，目前还没有天然肽可以穿过血脑屏障（BBB）的报道。本研究的目的是确定血脑屏障转运肽在原位小鼠灌流实验。根据已报道的血脑屏障转运化合物Gly-N甲基化Gly（Gly-Sar）的结构特点，合成了18个二肽，并将其灌流于小鼠脑内2分钟。在合成的二肽中，Gly-Sar、Gly-Pro和Tyr-Pro分别以7.60 +/- 1.29、3.49 +/- 0.66和3.53 +/- 0.74 μ L/g.min的Ki值转运穿过BBB，并在小鼠脑实质中积累。此外，使用MALDI-MS/MS成像分析的Tyr-Pro灌注的大脑，我们提供的证据Tyr-Pro积累在海马，下丘脑，纹状体，大脑皮层，小脑的小鼠大脑。
Apart from nutrients required for the brain, there has been no report that naturally occurring peptides can cross the blood-brain barrier (BBB). The aim of this study was to identify the BBB-transportable peptides using in situ mouse perfusion experiments. Based on the structural features of Gly-Nmethylated Gly (Gly-Sar), a reported BBB-transportable compound, 18 dipeptides were synthesized, and were perfused in the mouse brain for two minutes. Among the synthesized dipeptides, Gly-Sar, Gly-Pro, and Tyr-Pro were transported across the BBB with K-i values of 7.60 +/- 1.29, 3.49 +/- 0.66, and 3.53 +/- 0.74 mu L/g.min, respectively, and accumulated in the mouse brain parenchyma. Additionally, using MALDI-MS/MS imaging analysis of Tyr-Pro-perfused brain, we provide evidence for Tyr-Pro accumulation in the hippocampus, hypothalamus, striatum, cerebral cortex, and cerebellum of mouse brain.