| Item type |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2025-01-22 |
| タイトル |
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|
タイトル |
Identification of cyclic peptides for facilitation of transcellular transport of phages across intestinal epithelium in vitro and in vivo |
|
言語 |
en |
| 言語 |
|
|
言語 |
eng |
| キーワード |
|
|
主題 |
Cyclic peptide Intestinal absorption, Macromolecular drugs, Phage display technology |
| 資源タイプ |
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|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
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資源タイプ |
journal article |
| アクセス権 |
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アクセス権 |
open access |
|
アクセス権URI |
http://purl.org/coar/access_right/c_abf2 |
| 著者 |
Shunsuke, Yamaguchi
Shingo, Ito
Mio, Kurogi-Hirayama
Sumio, Ohtsuki
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| 内容記述 |
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内容記述タイプ |
Abstract |
|
内容記述 |
Methodology to enhance intestinal absorption of macromolecular drugs is an important challenge for developing next-generation biomedicines. So far, various cationic cell-penetrating peptides have been reported to facilitate uptake of certain bioactive proteins. However, cyclic peptides might be better candidates, as they are more metabolically stable than linear peptides. Accordingly, we hypothesized that suitable cyclic peptides would promote the absorption of macromolecules across intestinal epithelium. To test this idea, we adopted Caco-2 cell permeability assay as an in vitro human intestinal absorption model, and M13 phage as a model of macromolecules. Successive screenings of a phage library displaying cyclic heptapeptides via a short GGGS linker yielded 3 hits. Among them, phage displaying cyclic heptapeptide DNPGNET (DNP-phage) showed the greatest permeability across a Caco-2 cell monolayer and mouse intestinal epithelium. Interestingly, DNPGNET (DNP) does not contain any basic amino acids. Its isoelectric point (pI) was estimated to be 2.72. It did not reduce the viability or tight-junction integrity of Caco-2 cells at concentrations up to 100 μM for 24 h. Uptake of either DNP-phage or a fluorescence-labeled DNP derivative (AC-DNPGNET-CGGGS modified with 5/6-FAM at the C-terminal; the cysteines serve to generate the cyclic peptide via disulfide bond formation, and GGGS is the phage linker) by Caco-2 cells was inhibited by low temperature, unlabeled AC-DNPGNET-CGGGS and EIPA, a macropinocytosis inhibitor. Thus, DNP appears to facilitate transcellular permeability of phages via macropinocytosis, but not paracellular diffusion. These findings indicate that DNP is a promising candidate as a carrier to promote intestinal absorption of macromolecular drugs. |
| bibliographic_information |
en : Journal of Controlled Release
巻 262,
p. 232-238,
発行年 2017-09-28
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| item_16_source_id_7 |
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収録物識別子 |
0168-3659 |
| item_16_relation_11 |
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関連タイプ |
isVersionOf |
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|
関連識別子 |
https://doi.org/10.1016/j.jconrel.2017.07.037 |
| 権利 |
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|
権利情報 |
(C) 2017 Elsevier B.V. All rights reserved. |
| 権利 |
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|
権利情報 |
This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| 出版タイプ |
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出版タイプ |
AM |
|
出版タイプResource |
http://purl.org/coar/version/c_ab4af688f83e57aa |
| 出版者 |
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|
出版者 |
Elsevier |
10.1016_j.jconrel.2017.07.037.pdf (1.5 MB)
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