Dual-targeting anti-angiogenic cyclic peptides as potential drug leads for cancer therapy

Chan, LaiYue, Craik, David J. and Daly, Norelle L. (2016) Dual-targeting anti-angiogenic cyclic peptides as potential drug leads for cancer therapy. Scientific Reports, 6 . doi:10.1038/srep35347


Author Chan, LaiYue
Craik, David J.
Daly, Norelle L.
Title Dual-targeting anti-angiogenic cyclic peptides as potential drug leads for cancer therapy
Journal name Scientific Reports   Check publisher's open access policy
ISSN 2045-2322
Publication date 2016-10-13
Sub-type Article (original research)
DOI 10.1038/srep35347
Open Access Status DOI
Volume 6
Total pages 13
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Formatted abstract
Peptide analogues derived from bioactive hormones such as somatostatin or certain growth factors have great potential as angiogenesis inhibitors for cancer applications. In an attempt to combat emerging drug resistance many FDA-approved anti-angiogenesis therapies are co-administered with cytotoxic drugs as a combination therapy to target multiple signaling pathways of cancers. However, cancer therapies often encounter limiting factors such as high toxicities and side effects. Here, we combined two anti-angiogenic epitopes that act on different pathways of angiogenesis into a single non-toxic cyclic peptide framework, namely MCoTI-II (Momordica cochinchinensis trypsin inhibitor-II), and subsequently assessed the anti-angiogenic activity of the novel compound. We hypothesized that the combination of these two epitopes would elicit a synergistic effect by targeting different angiogenesis pathways and result in improved potency, compared to that of a single epitope. This novel approach has resulted in the development of a potent, non-toxic, stable and cyclic analogue with nanomolar potency inhibition in in vitro endothelial cell migration and in vivo chorioallantoic membrane angiogenesis assays. This is the first report to use the MCoTI-II framework to develop a 2-in-1 anti-angiogenic peptide, which has the potential to be used as a form of combination therapy for targeting a wide range of cancers.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Institute for Molecular Bioscience - Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 6 times in Thomson Reuters Web of Science Article | Citations
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