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

被引：50

作者：

Tanaka, Mitsuru ^{[1
]}

Dohgu, Shinya ^{[2
]}

Komabayashi, Genki ^{[1
]}

Kiyohara, Hayato ^{[1
]}

Takata, Fuyuko ^{[2
]}

Kataoka, Yasufumi ^{[2
]}

Nirasawa, Takashi ^{[3
]}

Maebuchi, Motohiro ^{[4
]}

Matsui, Toshiro ^{[1
]}

机构：

[1] Kyushu Univ, Fac Agr, Dept Biosci & Biotechnol, Grad Sch,Nishi Ku, 744 Motooka, Fukuoka, Fukuoka 8190395, Japan

[2] Fukuoka Univ, Fac Pharmaceut Sci, Dept Pharmaceut Care & Hlth Sci, Jonan Ku, 8-19-1 Nanakuma, Fukuoka, Fukuoka 8140180, Japan

[3] Bruker Japan KK, Kanagawa Ku, 3-9 Moriya Cho, Yokohama, Kanagawa 2210022, Japan

[4] FUJI OIL CO Ltd, Res & Dev Div, 1 Sumiyoshi Cho, Izumisano, Osaka 5988540, Japan

来源：

SCIENTIFIC REPORTS | 2019年 / 9卷 / 1期

关键词：

ANGIOTENSIN-CONVERTING ENZYME; TRP-HIS; PEPTIDES; PEPT2; MOUSE; ENTRY; ANATOMY; DISEASE;

D O I：

10.1038/s41598-019-42099-9

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

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-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.

引用

页数：10

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