論文 - 詳細
| RRC ID | 62784 |
|---|---|
| 著者 | Toyama K, Mizuguchi T, Nomura W, Tamamura H. |
| タイトル | Functional evaluation of fluorescein-labeled derivatives of a peptide inhibitor of the EGF receptor dimerization. |
| ジャーナル | Bioorg Med Chem |
| Abstract |
A cyclic decapeptide (1, ), which acts on the extracellular region of the EGF receptor, preventing it from dimerizing, has been developed. Peptide 2, which was labeled with fluorescein at the N-terminus of peptide 1, was synthesized based on structure-activity relationship studies. Peptide 2 essentially retained the inhibitory activity of peptide 1 against the receptor autophosphorylation. Confocal microscopy studies revealed that in carcinoma cells, the fluorescence of peptide 2 was localized inside some vesicles. Treatment of intact cells by peptide 1 in combination with peptide 2 decreased the fluorescence intensity significantly compared to treatment with only peptide 2. These results indicate that peptide 2 competes with peptide 1 for binding to the cellular surface. Six derivatives of peptide 2, in which constituent amino acids, with the exception of two cysteines and proline were randomized, were synthesized and used to treat the cells. Peptides 6 and 9 showed the highest fluorescence intensity in cells. From the results of the EGF receptor autophosphorylation assay, these two derivatives were proven to have higher inhibitory activity than peptide 2, which would therefore be a useful delivery peptide and fluorescent probe to find new inhibitors against the EGF receptor. Peptides 6 and 9 are promising leads for EGF receptor inhibitors. |
| 巻・号 | 24(16) |
| ページ | 3406-12 |
| 公開日 | 2016-8-15 |
| DOI | 10.1016/j.bmc.2016.05.026 |
| PII | S0968-0896(16)30350-9 |
| PMID | 27283787 |
| MeSH | Amino Acid Sequence Cell Line, Tumor Chromatography, High Pressure Liquid Dimerization ErbB Receptors / metabolism* Fluorescein / chemistry* Humans Peptides / chemistry Peptides / pharmacology* Spectrometry, Mass, Electrospray Ionization |
| IF | 3.073 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | A431(RCB0202) A549(RCB0098) |