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Multimeric Forms of Tyr-Ile-Gly-Ser-Arg (YIGSR) Peptide Enhance the Inhibition of Tumor Growth and Metastasis

Laboratory of Developmental Biology, National Institute of Dental Research, NIH, Bethesda, Maryland 20892

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)₁₆K₈K₄K₂KG] (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.

¹ To whom requests for reprints should be addressed, at Laboratory of Developmental Biology, National Institute of Dental Research, NIH, Bldg. 30, Room 427, 9000 Rockville Pike, Bethesda, MD 20892.

Received 4/21/93. Accepted 6/16/93.

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