ml9b00339_si_001.pdf (5.3 MB)
Inhibitory Effects of Multivalent Polypeptides on the Proliferation and Metastasis of Breast Cancer Cells
journal contribution
posted on 2019-11-14, 19:39 authored by Zhuangzhuang Zhang, Yachao Li, Huayu Wu, Xiao Zhang, Dan Zhong, Yahui Wu, Xianghui Xu, Jun Yang, Zhongwei GuThe 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.