Kakiuchi M, Izuno Y, Maeda M, Ueda K, Fujiwara K, Kunitada S, Kawasaki K
Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Japan.
Chem Pharm Bull (Tokyo). 1996 May;44(5):1107-10. doi: 10.1248/cpb.44.1107.
Fibrinogen-related peptides, monomeric cyclic peptides through a disulfide bond [cyclo(H-Cys-Arg-Gly-Asp-Phe-Cys-NH2), cyclo(H-Cys-Arg-Gly-Asp-Phe-Cys-Gly-NH2), cyclo(H-Cys-Arg-Gly-Asp-Cys-NH2) and cyclo(H-Cys-Arg-Gly-Asp-Cys-Gly-NH2)], were prepared by the solid phase method with disulfide bond formation on the solid support. The acetamidomethyl group was used for protection of the thiol group of Cys and synthetic peptide-resins were treated with iodine to give the disulfide bond. Monomeric cyclic peptides were obtained as main products. Purified S-acetamidomethylated peptides were also oxidized with iodine, but the desired materials could not be isolated by HPLC. The disulfide formation from S-acetamidomethylcysteine-containing peptide resin by iodine treatment on the solid support was more effective than that from S-acetamidomethylcysteine-containing peptide. The inhibitory effect of the cyclic peptides on platelet aggregation were much more potent than that of H-Arg-Gly-Asp-NH2.
通过在固相载体上形成二硫键制备了纤维蛋白原相关肽，即单体环肽[环（H-半胱氨酸-精氨酸-甘氨酸-天冬氨酸-苯丙氨酸-半胱氨酸-NH2）、环（H-半胱氨酸-精氨酸-甘氨酸-天冬氨酸-苯丙氨酸-半胱氨酸-甘氨酸-NH2）、环（H-半胱氨酸-精氨酸-甘氨酸-天冬氨酸-半胱氨酸-NH2）和环（H-半胱氨酸-精氨酸-甘氨酸-天冬氨酸-半胱氨酸-甘氨酸-NH2）]。乙酰氨基甲基用于保护半胱氨酸的巯基，合成肽树脂用碘处理以形成二硫键。以单体环肽作为主要产物。纯化的S-乙酰氨基甲基化肽也用碘氧化，但无法通过高效液相色谱法分离出所需物质。在固相载体上通过碘处理由含S-乙酰氨基甲基半胱氨酸的肽树脂形成二硫键比由含S-乙酰氨基甲基半胱氨酸的肽形成二硫键更有效。环肽对血小板聚集的抑制作用比H-精氨酸-甘氨酸-天冬氨酸-NH2强得多。
