文章基本信息

标题：Brain-transportable dipeptides across the blood-brain barrier in mice
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作者：Mitsuru Tanaka ; Shinya Dohgu ; Genki Komabayashi 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2019
卷号：9
期号：1
页码：1-10
DOI：10.1038/s41598-019-42099-9
出版社：Springer Nature
摘要：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-N-methylated 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 Ki values of 7.60 ± 1.29, 3.49 ± 0.66, and 3.53 ± 0.74 µL/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.