70 RGDSPASS残基を含むフィブロネクチン関連シスチンペプチドのターン構造(ポスター発表の部)

概要

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The Arg-Gly-Asp-Ser (RGDS) sequence is an active site in the cell binding domain of fibronectin (FN), cell adhesion protein. It also exists in some bioactive proteins and is predicted to be an important sequence for biological activity. Previously, we reported that Pro-Ala-Ser-Ser (PASS), located adjacent to the RGDS toward the C-terminal in FN, participated in cell binding and cell migration. We are interested in the secondary structure of the RGDSPASS sequence of FN. We designed three types of RGDSPASS containing peptides and synthesized FR-1, FR-2 and FR-3. These cyclic peptides exhibited high activity as a platelet aggregation inhibitor. The assay was carried out using rabbit platelet rich plasma. IC_<50> of FR-1, FR-2, and FR-3 were 67, 280, and 135μM, respectively. Their secondary structures were determined by NMR using NOESY and the H-D exchange of the amide protons. We found that both RGDS and PASS have an antiparallel location in cyclic peptides, FR-1 and FR-3, which exhibit high activity as a platelet aggregation inhibitor. The fibrinogen receptor on the platelet surface is able to recognize the unique structure of RGDSPASS within this sequence containing peptides. The above results suggest that the structure of FR-1 is appropriate for binding it to the fibrinogen receptor, and the structure corresponds to that of the active site of FN.
1993-09-10