Type

Journal Article

Authors

Kevin E O'Connor
Qun Ren Zulian
Manfred Zinn
Shane T Kenny
Ramesh Babu
William M Gallagher
Norma O'Donovan
Marc Devocelle
Annette T Byrne
Aisling O'Connor
and 3 others

Subjects

Biochemistry

Topics
hela cells anti microbial anti cancer chain length apoptosis peptide cancer cells conjugated peptides

The anti-cancer activity of a cationic anti-microbial peptide derived from monomers of polyhydroxyalkanoate. (2012)

Abstract 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 terminally hydroxylated decanoic acid (ω-hydroxydecanoic acid) exhibited 3.3 and 6.3 fold higher IC(50) values compared to R10 conjugated peptide indicating a role for the position of the hydroxyl moiety in enhancement of anti-cancer activity. Conjugation of decanoic acid (C10) to peptides resulted in similar or higher IC(50) values compared to R10 conjugates but C10 conjugates did not exhibit any cancer selectivity. Combination studies showed that R10DP18L exhibited synergy with cisplatin, gemcitabine, and taxotere with IC(50) values in the nanomolar range.
Collections Ireland -> University College Dublin -> PubMed

Full list of authors on original publication

Kevin E O'Connor, Qun Ren Zulian, Manfred Zinn, Shane T Kenny, Ramesh Babu, William M Gallagher, Norma O'Donovan, Marc Devocelle, Annette T Byrne, Aisling O'Connor and 3 others

Experts in our system

1
Kevin E O'Connor
University College Dublin
Total Publications: 52
 
2
Shane T Kenny
University College Dublin
Total Publications: 15
 
3
Ramesh P Babu
University College Dublin
Total Publications: 11
 
4
William M Gallagher
University College Dublin
Total Publications: 148
 
5
Norma O'Donovan
Dublin City University
Total Publications: 59
 
6
Marc Devocelle
Royal College of Surgeons in Ireland
Total Publications: 65
 
7
Annette T Byrne
Royal College of Surgeons in Ireland
Total Publications: 41