Open AccessInhibitory Effects of Multivalent Polypeptides on the Proliferation and Metastasis of Breast Cancer Cells
Author(s) -
Zhuangzhuang Zhang,
Yachao Li,
Huayu Wu,
Xiao Zhang,
Di Zhong,
Yigen Wu,
Xianghui Xu,
Jun Yang,
Zhongwei Gu
Publication year - 2019
Publication title -
acs medicinal chemistry letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 66
ISSN - 1948-5875
DOI - 10.1021/acsmedchemlett.9b00339
Subject(s) - peptide , metastasis , in vitro , chemistry , dendrimer , cancer research , cytotoxicity , proteolysis , cancer cell , in vivo , metastasis suppressor , microbiology and biotechnology , biochemistry , cancer , biology , enzyme , genetics
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.