End-functionalised glycopolymers as glycosaminoglycan mimetics inhibit HeLa cell proliferation
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Authors
Yang, Chendong
Gao, Lei
Shao, Meng
Cai, Chao
Wang, Lihao
Chen, Yifan
Li, Jianghua
Fan, Fei
Han, Yubing
Liu, Ming
Issue Date
2020-08-07
Type
Article
Language
ENG
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Alternative Title
Abstract
The glycosaminoglycans (GAGs) on cell surfaces play significant roles during cancer development, and the heparanase activity is strongly implicated in the structural remodeling of the extracellular GAG matrix, potentially leading to tumour cell invasion. Polymer–protein/peptide conjugates are one of the most promising approaches for anticancer therapy due to their controllability, biocompatibility, and targeting properties. In this study, distinct and well-defined glycopolymer–peptide conjugates, mimicking the multivalent architecture found in GAGs, were synthesised for targeting and killing tumour cells. Regio-selectively sulphated galactosamine derivatives were chemically synthesised, and six GAGs-mimetic glycopolymers were generated by post-modification based on the ring-opening metathesis polymerization (ROMP). The glycopolymers with diverse galactosamine sulphation patterns showed significant inhibitory effects on heparanase. Glycopolymers decorated with 3,4,6-O-sulphated GalNAc exhibited the highest activities, inhibiting heparanase as well as tumour cell proliferation. We demonstrated that a novel glycopeptide mimetic, derived from end-functionalised conjugation of the iRGD peptide on the glycopolymer, could effectively enter HeLa cells and inhibit signalling pathways involved in tumour cell proliferation. These findings should promote the development of novel glycomimetics for specific tumour-targeted therapies.
Description
Polymer Chemistry, 11, 4714
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Full Citation
End-functionalised glycopolymers as glycosaminoglycan mimetics inhibit HeLa cell proliferation, C. Yang, L. Gao, C. Cai, L. Wang, M. Shao, F. Fan, J. Li, M. Liu, R. J. Linhardt, G. Yu, Polymer Chemistry, 11, 4714, 2020.
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Volume
Issue
PubMed ID
DOI
ISSN
17599962
17599954
17599954