Basic research of new local treatment for inflammatory diseases using molecular-targeting chimera peptide

分子靶向嵌合肽局部治疗炎症性疾病的基础研究

• 批准号: 21790111
• 负责人: KOHNO Masayuki
• 金额: $ 2.66万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21790111/
• 关键词: 医薬分子設計; ペプチド創薬; 分子標的; 局所投与; DDS

We investigated the possibility of new powerful therapy for inflammatory diseases using chimera peptides that have a binding sequence to inflammatory cytokine receptors and an adhesion sequence to cell membrane without cytotoxic activity.As a result of pre-survey, we selected TNFα, TLR4, and TGFβ1 as the target molecules, and determined the promising candidates among various antagonist peptides and chimera peptides by the in vitro assay systems. Inhibitory effect of TNFα-antagonist peptide was increased by chimera conjugation with a membrane-adhesion sequence. Local treatment of TGFβ1-antagonist peptide by intratracheal nebulization decreased the levels of fibrotic factors in lung tissue in bleomycin-induced lung fibrosis rat model.

本研究以TNFα、TLR4和TGFβ1为靶分子，通过体外实验系统筛选出具有抗炎性细胞因子受体结合序列和细胞膜粘附序列的嵌合肽作为治疗炎症性疾病的有效靶分子。TNFα拮抗肽的抑制作用通过与膜粘附序列的嵌合体缀合而增强。肺内雾化吸入TGFβ1拮抗肽可降低博莱霉素诱导的肺纤维化大鼠模型肺组织中纤维化因子的水平。

项目成果

A novel EGFR-targeted hybrid peptide can overcome the resistance of cancer cells to tyrosine kinase inhibitors.

一种新型 EGFR 靶向杂合肽可以克服癌细胞对酪氨酸激酶抑制剂的耐药性。

• 发表时间: 2010
• 作者: Masayuki Kohno;Tomohisa Horibe;Yoshiaki Yano;Katsumi Matsuzaki;Koji Kawakami.
• 通讯作者: Koji Kawakami.

A novel hybrid peptide targeting EGFR-expressing cancers

• DOI: 10.1016/j.ejca.2010.10.021
• 发表时间: 2011-03-01
• 期刊: EUROPEAN JOURNAL OF CANCER
• 影响因子: 8.4
• 作者: Kohno, Masayuki;Horibe, Tomohisa;Kawakami, Koji
• 通讯作者: Kawakami, Koji

DESIGN OF A NOVEL EGFR-TARGETED HYBRID-PEPTIDE AND CHARACTERIZATION OF ITS CYTOTOXIC MECHANISM IN CANCER CELL

新型 EGFR 靶向杂合肽的设计及其在癌细胞中的细胞毒机制的表征

• 发表时间: 2009
• 作者: Fujii S.;Yamada A.;Ohta K.;Endo Y.;Kagechika H.;河野雅之
• 通讯作者: 河野雅之