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.

Laminin-related peptide poly(ethylene glycol) hybrid, Tyr-Ile-Gly-Ser-Arg-aminopoly(ethylene glycol) was prepared by the solution method and carboxylated poly(ethylene glycol)-Tyr-Ile-Gly-Ser-Arg was prepared by the solid phase method. Their inhibitory effects on experimental tumor metastasis were examined in mice. The inhibitory effect of Tyr-Ile-Gly-Ser-Arg was significantly potentiated by hybrid formation with poly(ethylene glycol) either at amino- or carboxyl terminals of the peptide. Of the hybrids, Tyr-Ile-Gly-Ser-Arg-amino(polyethylene glycol) #6000 hybrid exhibited about 10 times more potent anti-metastatic effect than the peptide itself. The inhibitory effect of a mixture of the carboxylated poly(ethylene glycol) hybrid and Arg-Gly-Asp-aminopoly(ethylene glycol) hybrid also exhibited an inhibitory effect.

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