| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1997: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
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| Research Abstract |
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
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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
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