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Developing of fibronectin-derived RGD peptide as a molecular imaging probe
https://repo.qst.go.jp/records/69761
https://repo.qst.go.jp/records/69761dbf42876-98af-4bae-9bf8-d0e797a52bcf
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2009-05-27 | |||||
| タイトル | ||||||
| タイトル | Developing of fibronectin-derived RGD peptide as a molecular imaging probe | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_c94f | |||||
| 資源タイプ | conference object | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Jin, Zhao-Hui
× Jin, Zhao-Hui× Furukawa, Takako× Saga, Tsuneo× Fujibayashi, Yasuhisa× et.al× 金 朝暉× 古川 高子× 佐賀 恒夫 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | There has been increasing interest in the development of arginine-glycine-aspartic acid (RGD) peptides for tumor imaging and therapy, targeted drug delivery, biomaterial research for tissue engineering and transplant implantation, via the interaction between RGD ligand and integrin receptor. Here, we report the development of fibronectin (FN)-derived RGD peptides in terms of 3 parameters: (1) the amino acid environment adjacent to the RGD, (2) the divalent cation regulation, and (3) the polyvalency effect. Derived from FN sequence, a range of linear RGD peptides including RGDY, GRGDSY, AVTGRGDSY, AVTGRGDSPASSKY, together with a control peptide GRGESY, were synthesized and radiolabeled with 125I for cell-binding assay. The AVTGRGDSY showed the highest binding to the human embryonic kidney cells HEK293(beta1) (overexpressing beta1 integrin subunit) and HEK293(beta3) (overexpressing alphaVbeta3 integrin) in a divalent cation-independent and divalent cation (Mn2+)-dependent manner, respectively. We subsequently designed and synthesized the di- and tri-meric AVTGRGDSY peptides. Multimerization resulted in a diminished binding to HEK293(beta1), but greatly improved the binding to alphaVbeta3-positive cells in the presence of Mn2+ compared to Ca2+ and Mg2+. In vitro blocking study, together with integrin expression profiles analysis, confirmed that both of the dimer and trimer were highly specific for alphaVbeta3, with comparable binding affinity as that of alphaVbeta3-targeting cyclo (RGDfV) peptide. Optical imaging of subcutaneous HEK293(beta3) tumor-bearing mice using near infrared dye Cy5.5-labeled dimer showed good tumor-to-background contrast, and in vitro this conjugate was localized onto cell membrane and also internalized. This study demonstrates important molecular features of FN-derived AVTGRGDSY peptides. The multimeric AVTGRGDSY peptide would be a promising alphaVbeta3-targeting molecular probe. | |||||
| 会議概要（会議名, 開催地, 会期, 主催者等） | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | 第４回日本分子イメージング学会 | |||||
| 発表年月日 | ||||||
| 日付 | 2009-05-15 | |||||
| 日付タイプ | Issued | |||||
