Inhibitory
Effects of Multivalent Polypeptides on
the Proliferation and Metastasis of Breast Cancer Cells
Zhuangzhuang Zhang
Yachao Li
Huayu Wu
Xiao Zhang
Dan Zhong
Yahui Wu
Xianghui Xu
Jun Yang
Zhongwei Gu
10.1021/acsmedchemlett.9b00339.s001
https://acs.figshare.com/articles/journal_contribution/Inhibitory_Effects_of_Multivalent_Polypeptides_on_the_Proliferation_and_Metastasis_of_Breast_Cancer_Cells/10308044
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 <i>in
vitro</i> 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 <i>in vivo</i> 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.
2019-11-14 19:39:49
tumor cell metastasis
octavalent YSL dendrimers
4 T 1 tumors
BALB
YSL dendrimers
peptide drugs
Breast Cancer Cells
vivo antitumor activity