The anti-cancer activity of a cationic anti-microbial peptide derived from monomers of polyhydroxyalkanoate

Authors: Stephen O’Connor, Emilia Szwej, Jasmina Nikodinovic-Runic, Aisling O’Connor, Annette T Byrne, Marc Devocelle, Norma O’Donovan, William M Gallagher, Ramesh Babu, Shane T Kenny, Kevin E O’Connor

Publication Date: 01/04/2013

Journal: Biomaterials

Volume: 34

Issue: 11

Pages: 2710-2718

Publisher: Elsevier

The biodegradable polymer medium chain length polyhydroxyalkanoate (mclPHA), produced by Pseudomonas putida CA-3, was depolymerised and the predominant monomer (R)-3-hydroxydecanoic acid (R10) purified. R10 was conjugated to a d-peptide DP18 and its derivatives. All peptides conjugated with R10 exhibited greater anti-cancer activity compared to the unconjugated peptides. Unconjugated and conjugated peptides were cytocidal for cancer cells. Conjugation of R10 to peptides was essential for enhanced anti-proliferation activity, as unconjugated mixes did not result in enhancement of anti-cancer activity. The conjugation of R10 resulted in more rapid uptake of peptides into HeLa and MiaPaCa cells compared to unconjugated peptide. Both unconjugated and R10 conjugated peptides localized to the mitochondria of HeLa and MiaPaCa cells and induced apoptosis. Peptide conjugated with a …

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