1998 Fiscal Year Final Research Report Summary
Study on peptides passing through cell membranes by the electrostatic interaction.
| Project/Area Number |
09680581
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Bioorganic chemistry
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| Research Institution | Kinki University |
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Principal Investigator |
WAKAMIYA Tateaki Kinki University, 理工学部, 教授 (10028243)
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| Project Period (FY) |
1997 – 1998
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| Keywords | Peptide / Blood-brain barrier / Electrostatic interaction / Adsorptive-mediated transcytosis / TRH / Kyotorphin / p-Boronophenylalanine / Neutron capture therapy |
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| Research Abstract |
The blood-brain barrier (BBB) is a highly selective membranous barrier regulating the transport of substances in blood into the brain parenchyma. Recently we succeeded to open away to deliver synthetic peptides into the brain by the adsorptive-mediated transcytosis (AMT) which is based on the electrostatic interaction between the cationic ligands and the anionic sites on the cell membranes. For example, a synthetic cationic peptide MeTyr-Arg-MeArg-D-Leu-NH(CH_2)_8 termed OO1-C8 was highly transported through the BBB via the AMTmechanism. In the present research project, we prepared a fluorescence-labeled peptide 001-C8-NBD (NBD : 5-nitrobenzo-3-oxa-2, 4-diazole) which was successfully applied to elucidate and visualize the process of AMT in Caco-2 cells by measuring the transepithelial transport of fluorescent 0O1-C8-NBD, as well as by visual three-dimentional analysis of living, nonfixed cells by confocal laser microscopy.
We next synthesized both the tyrotropic hormone releasing hormone (TRH) and an analgesic peptide kyotorphin (KYO) analogs in which the octanediamine (Oda=C8) and NBD residues were introduced ; these peptides were designed as possessing suitable cationic and lipophilic character requiring for the BBB transport by the AMT mechanism. So far we examined, TRH-C8-NBD was transported through the BBB by the passive transport mechanism but not the AMT mechanism, while KYO-C8-NBD did not pass through the BBB.This fact suggests that we need to reconsider for the design of the peptides passing through the BBB.
Furthermore, we prepraed three kinds of p-boronophenylalanine containing dipeptides which will be applied to the elucidation of neutron capture therapy of cancer cells.
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