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标题：Amino Acids and Peptides. XXIX. Synthesis and Antimetastatic Effects of Peptides and Peptide-Poly(Ethylene Glycol) Hybrids Related to the Core Sequence of the Type III Connecting Segment Domain of Fibronectin
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作者：Koichi KAWASAKI ; Mitsuko MAEDA ; Sachiye INOUE 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：1996
卷号：19
期号：12
页码：1574-1579
DOI：10.1248/bpb.19.1574
出版社：The Pharmaceutical Society of Japan
摘要：Peptides (H-Glu-Ile-Leu-Asp-Val-NH₂, H-Glu-Ile-Leu-Asp-Val-Pro-Ser-Thr-NH₂, H-Arg-Glu-Asp-Val-NH₂) and their poly(ethylene glycol)(PEG) hybrids related to the core sequence of the type III connecting segment domain of fibronectin A chain were prepared by the solution method or the solid phase method. Their inhibitory effects on the adhesion and migration of B16-BL6 melanoma cells to fibronectin were assessed in vitro, and their therapeutic potency against tumor metastasis were also examined. Anti-adhesive and anti-migrative effects of the synthetic fibronectin-related peptids were superior to those of their PEG hybrids, so we found that the in vitro bioactivity of peptides decreased by PEGylation. In the in vivo assay, we found that the synthetic peptides containing Glu-Ile-Leu-Asp-Val and Arg-Glu-Asp-Val sequences exhibited an inhibitory effect on the experimental metastasis of B16-BL6 melanoma. Of the synthetic peptides, H-Glu-Ile-Leu-Asp-Val-NH₂ exhibited the most potent inhibitory effect. Hybrid formation of Arg-Glu-Asp-Val with poly(ethylene glycol) resulted in potentiation of the inhibitory effect of the parent peptides. A mixture composed of PEG hybrids of Glu-Ile-Leu-Asp-Val, Arg-Glu-Asp-Val and Tyr-Ile-Gly-Ser-Arg dramatically inhibited tumor metastasis.
关键词：fibronectin;metastasis inhibitor;poly(ethylene glycol);peptide hybrid;poly(ethylene glycol) hybrid