TY - JOUR
T1 - Brain-transportable dipeptides across the blood-brain barrier in mice
AU - Tanaka, Mitsuru
AU - Dohgu, Shinya
AU - Komabayashi, Genki
AU - Kiyohara, Hayato
AU - Takata, Fuyuko
AU - Kataoka, Yasufumi
AU - Nirasawa, Takashi
AU - Maebuchi, Motohiro
AU - Matsui, Toshiro
N1 - Funding Information:
The authors are grateful to Ms K. Miyazaki at Kyushu University for her technical assistance. This study was supported in part by a grant-in-aid from the Ministry of Education, Science, Sports, and Culture of Japan (No. 18K05534 to M.T. and No. 17K19912 to T.M.).
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 -
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.
AB -
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.
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U2 - 10.1038/s41598-019-42099-9
DO - 10.1038/s41598-019-42099-9
M3 - Article
C2 - 30962462
AN - SCOPUS:85064052070
SN - 2045-2322
VL - 9
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 5769
ER -