Inhibitory Effects of Multivalent Polypeptides on the Proliferation and Metastasis of Breast Cancer Cells.

The susceptibility of peptide drugs to enzymatic degradation has limited their clinical applications. To overcome this limitation, we attached the peptide tyroserleutide (YSL) to a molecular scaffold in order to produce homogeneous monovalent, bivalent, tetravalent, and octavalent YSL dendrimers with highly ordered secondary structures. These multivalent YSL dendrimers were resistant to proteolysis and were better able to induce cytotoxicity in tumor cells in vitro as compared with monomeric peptides. These multivalent YSL dendrimers were also better able to constrain tumor cell metastasis. Compared with monovalent YSL, the multivalent YSL dendrimers displayed enhanced in vivo antitumor activity and suppressed tumor growth and metastasis in BALB/c mice bearing 4T1 tumors. These findings indicate that multivalence can significantly enhance ligand potency and represent a potential method for the development of peptide drugs with high therapeutic potential.