Multimeric forms of Tyr-Ile-Gly-Ser-Arg (YIGSR) peptide enhance the inhibition of tumor growth and metastasis.

Abstract

The Tyr-Ile-Gly-Ser-Arg (YIGSR) peptide derived from the laminin B1 chain has been shown to decrease tumor growth and metastasis. Utilizing the multimeric antigen peptide system assembled on a branched lysine core, we synthesized several sizes of multimeric YIGSR, (CH3CO-Tyr-Ile-Gly-Ser-Arg-Gly)16-Lys8-Lys4-Lys2 -Lys-Gly [(Ac-YIGSRG)16 K8K4K2KG] (designated Ac-Y16), (Ac-YIGSRG)8K4K2KG (Ac-Y8), and (Ac-YIGSRG)4K2KG (Ac-Y4), and related peptides, Ac-(YIGSRG)4-NH2 (Ac-Y4L) and Ac-YIGSR-NH2 (Ac-Y1) and evaluated their biological activities in inhibiting tumor growth and metastasis. Coinjection of 0.2 mg/mouse of Ac-Y16 i.v. with B16-F10 mouse melanoma cells inhibited lung colony formation by 97%, whereas 0.2 mg/mouse of Ac-Y1 inhibited by 50%. The larger the peptide (Ac-Y16 > Ac-Y8 > Ac-Y4 > Ac-Y1), the more inhibitory effect there was on lung metastasis. Ac-Y16 also inhibited the growth of s.c.-injected B16-F10 tumors. These data demonstrate that the multimeric YIGSR peptides strongly enhanced the activity of YIGSR in inhibiting tumor growth and metastasis and suggest that these compounds are potentially useful for clinical applications.

• Authors: M Nomizu, K Yamamura, H K Kleinman, Y Yamada
• Journal: Cancer research (Cancer Res) Vol. 53 Issue 15 Pg. 3459-61 (Aug 01 1993) ISSN: 0008-5472 [Print] United States
• PMID: 8339246 (Publication Type: Journal Article)

Chemical References

• Laminin
• Oligopeptides
• Peptides
• tyrosyl-isoleucyl-glycyl-seryl-arginine

Topics

• Amino Acid Sequence
• Animals
• Laminin (therapeutic use)
• Melanoma, Experimental (drug therapy, pathology, secondary)
• Mice
• Mice, Inbred C57BL
• Molecular Sequence Data
• Neoplasm Metastasis
• Oligopeptides (therapeutic use)
• Peptides (therapeutic use)
• Tumor Cells, Cultured