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Brain-transportable dipeptides across the blood-brain barrier in mice.

ABSTRACT: 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 K_i 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.

SUBMITTER: Tanaka M

PROVIDER: S-EPMC6453885 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Brain-transportable dipeptides across the blood-brain barrier in mice.

Tanaka Mitsuru M Dohgu Shinya S Komabayashi Genki G Kiyohara Hayato H Takata Fuyuko F Kataoka Yasufumi Y Nirasawa Takashi T Maebuchi Motohiro M Matsui Toshiro T

Scientific reports 20190408 1

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 ...[more]

PMID: 30962462

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