SYNTHESIS AND EVALUATION OF OLIGOPEPTIDES EXHIBITING CELL-ATTACHMENT ACTIVITY.

具有细胞附着活性的寡肽的合成和评估。

• 批准号: 08680942
• 负责人: HIRANO Yoshiaki
• 金额: $ 1.28万
• 依托单位: FUCULTY OF ENGINEERING,OSAKA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08680942/
• 关键词: Cell-attachment oligopeptides; RGDS; poly (RGDS); RGDS mimetic peptide; Conformational analysis; Molecular mechanics; Inhibition of platelet aggregation; Structure-activity relationship; 医用材料; 構造活性相関; 機能構造活性相関; ハイブリッド材料

Recent progress in the structure and bioactivity elucidation of such extracellular, structural proteins as fibronectin, vitronectin, and collagen has provide information on the cell attachment sites of these proteins. Tetrapeptides Arg-Gly-Asp-Xaa (Xaa=Ser, Val, Ala and Thr) were suggested to be the cellular recognition determinants of fibronectin, vitronectin, and collagen, respectively.In this work, Arg-Gly-Asp-Ser (RGDS) related molecules and RGDS mimetic peptide were synthesized for the purpose of improving the cell attachment activities of RGDS oligopeptide, and their cell-attachment activities were assayd by cell-inhibition method, cell-attachment method and inhibition of platelet aggregation method. Moreover, theoretical conformation analysis was carried out for Ac-Arg-Gly-Asp-Ser-NHMe and Ac-(Arg-Gly-Asp-Ser)_8-NHMe, using ECEPP and conformational energy minimization procedure.The cell attachment property of L-929 cell to fibronectin coated substrate was more specifically inhib … More ited by adding (RGDS)_n than adding RGDS oligopeptide. Activity of cell attachment depends on the molecular weight of poly (RGDS). The platelet aggregation property was more specifically inhibited by RGDS and RGDS mimetic peptids.The tetrapeptide Ac-Arg-Gly-Asp-Ser-NHMe was represented by an ensemble composed of many stable conformations. The lowest-energy backbone conformation is an alpha-helical conformation. According to the calculation, Ac-Arg-Gly-Asp-Ser-NHMe is stabilized by three kinds of hydrogen bondings and takes non-bend structure. The guanidino residue of Arg locates at the opposite side of the carbonyl group of Asp.The lowest-energy conformation of Ac-(Arg-Gly-Asp-Ser)_8-NHMe is a right-handed alpha-helical conformation having six types of hydrogen-bonds. All side-chain groups of Arg, Asp and Ser are exposed to the outside of helix. These result suggested that side chains locate in the suitable position for playing the importance role as the ligand for the cell surface receptor. Less

最近的进展，在结构和生物活性阐明这样的细胞外，结构蛋白质，如纤连蛋白，玻连蛋白，胶原蛋白提供了这些蛋白质的细胞附着位点的信息。四肽Arg-Gly-Asp-Xaa Xaa=Ser，瓦尔，Ala和Thr分别是纤维连接蛋白、玻连蛋白和胶原蛋白的细胞识别决定簇，为了提高RGDS寡肽的细胞粘附活性，合成了Arg-Gly-Asp-Ser（RGDS）相关分子和RGDS模拟肽，并用细胞抑制法测定了它们的细胞粘附活性，细胞附着法和抑制血小板聚集法。此外，采用ECEPP和构象能量最小化法对Ac-Arg-Gly-Asp-Ser-NHMe和Ac-（Arg-Gly-Asp-Ser）_8-NHMe进行了理论构象分析，结果表明，L-929细胞在纤连蛋白包被的底物上的粘附特性更具有特异性。 ...更多信息 加入（RGDS）_n比加入RGDS寡肽效果更好。细胞粘附的活性取决于聚（RGDS）的分子量。RGDS和RGDS模拟肽对血小板聚集的抑制作用更强，四肽Ac-Arg-Gly-Asp-Ser-NHMe表现为一个由多种稳定构象组成的体系。最低能量的骨架构象是α-螺旋构象。计算表明，Ac-Arg-Gly-Asp-Ser-NHMe是由三种氢键稳定的，呈非弯曲结构。Ac-（Arg-Gly-Asp-Ser）_8-NHMe的最低能量构象为右旋α-螺旋构象，有6种氢键。Arg、Asp和Ser的所有侧链基团暴露于螺旋的外部。这些结果表明，侧链位于合适的位置，作为细胞表面受体的配体发挥重要作用。少

项目成果

Y.Hirano, 他3名: "Theoretical Conformational Analysis of Cyclic Oligopeptide Cys-Arg-Gly-Asp-Cys with Disultide Linkage." Biomedical Materials Research in the Far East. 3. 32-33 (1997)

Y. Hirano 等 3 人：“具有二硫键的环状寡肽 Cys-Arg-Gly-Asp-Cys 的理论构象分析。远东生物医学材料研究”3. 32-33 (1997)。

Y.Hirano, 他3名: "Conformational Analysis of Cell-Attachment Model Pepticles" Biomedical Materials Research in the Far East. 3. 92-93 (1997)

Y. Hirano 等 3 人：“细胞附着模型 Pepticles 的构象分析”远东生物医学材料研究 3. 92-93 (1997)。

Y.Hirano, 他5名: "Theoretical Analysis on Helical Structures of poly (Xaa-Pro-Pro)" Reports on Progress in Polymer Physics in Japan. 40(印刷中). (1998)

Y.Hirano 等 5 人：“聚 (Xaa-Pro-Pro) 螺旋结构的理论分析”日本高分子物理学进展报告 40（出版中）。

Y.Hirano 他3名: "Conformational Analysis of Cell-Attachment Model Peptides" Biomedical Materials Research in the Far East. 3. 92-93 (1997)

Y. Hirano 和其他 3 人：“细胞附着模型肽的构象分析”远东生物医学材料研究 3. 92-93 (1997)。

M.Hattori 他4名: "Theoretical Analysis on Helical Structure of Poly(Xaa-Pro-Pre)" Reports on Progress in Polymer Physics in Japan. 39(印刷中). (1998)

M. Hattori 等 4 人：“Poly(Xaa-Pro-Pre) 螺旋结构的理论分析”日本高分子物理学进展报告 39（出版中）。