TY  - JOUR
AU  - Szwej, Emilia
AU  - Devocelle, Marc
AU  - Kenny, Shane
AU  - Guzik, Maciej
AU  - O'Connor, Stephen
AU  - Nikodinović-Runić, Jasmina
AU  - Milovanović, Jelena
AU  - Maslak, Veselin
AU  - Byrne, Annete T.
AU  - Gallagher, William M.
AU  - Zulian, Qun Ren
AU  - Zinn, Manfred
AU  - O'Connor, Kevin 
PY  - 2015
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/877
AB  - Conjugation of DP18L peptide with (R)-3-hydroxydecanoic acid, derived from the biopolymer polyhydroxyalkanoate, enhances its anti-cancer activity (O'Connor et al., 2013. Biomaterials 34, 2710-2718). However, it is unknown if other (R)-3-hydroxyalkanoic acids (R3HA5) can enhance peptide activity, if chain length affects enhancement, and what effect R3HA5 have on peptide structure. Here we show that the degree of enhancement of peptide (DP18L) anti-cancer activity by R3HA5 is carbon chain length dependent. In all but one example the R3HA conjugated peptides were more active against cancer cells than the unconjugated peptides. However, R3HA5 with 9 and 10 carbons were most effective at improving DPI 8L activity. DPI 8L peptide variant DPI 7L, missing a hydrophobic amino acid (leucine residue 4) exhibited lower efficacy against MiaPaCa cells. Circular dichroism analysis showed DP17L had a lower alpha helix content and the conjugation of any R3HA ((R)-3-hydroxyhexanoic acid to (R)-3-hydroxydodecanoic acid) to DPI 7L returned the helix content back to levels of DPI 8L. However (R)-3-hydroxyhexanoic did not enhance the anti-cancer activity of DPI 7L and at least 7 carbons were needed in the R3HA to enhance activity of D17L. DP17L needs a longer chain R3HA to achieve the same activity as DP18L conjugated to an R3HA. As a first step to assess the synthetic potential of polyhydroxyalkanoate derived R3HA5, (R)-3-hydroxydecanoic acid was synthetically converted to (+/-)3-chlorodecanoic acid, which when conjugated to DP18L improved its antiproliferative activity against MiaPaCa cells.
PB  - Elsevier Science Bv, Amsterdam
T2  - Journal of Biotechnology
T1  - The chain length of biologically produced (R)-3-hydroxyalkanoic acid affects biological activity and structure of anti-cancer peptides
EP  - 12
SP  - 7
VL  - 204
DO  - 10.1016/j.jbiotec.2015.02.036
ER  - 

@article{
author = "Szwej, Emilia and Devocelle, Marc and Kenny, Shane and Guzik, Maciej and O'Connor, Stephen and Nikodinović-Runić, Jasmina and Milovanović, Jelena and Maslak, Veselin and Byrne, Annete T. and Gallagher, William M. and Zulian, Qun Ren and Zinn, Manfred and O'Connor, Kevin ",
year = "2015",
abstract = "Conjugation of DP18L peptide with (R)-3-hydroxydecanoic acid, derived from the biopolymer polyhydroxyalkanoate, enhances its anti-cancer activity (O'Connor et al., 2013. Biomaterials 34, 2710-2718). However, it is unknown if other (R)-3-hydroxyalkanoic acids (R3HA5) can enhance peptide activity, if chain length affects enhancement, and what effect R3HA5 have on peptide structure. Here we show that the degree of enhancement of peptide (DP18L) anti-cancer activity by R3HA5 is carbon chain length dependent. In all but one example the R3HA conjugated peptides were more active against cancer cells than the unconjugated peptides. However, R3HA5 with 9 and 10 carbons were most effective at improving DPI 8L activity. DPI 8L peptide variant DPI 7L, missing a hydrophobic amino acid (leucine residue 4) exhibited lower efficacy against MiaPaCa cells. Circular dichroism analysis showed DP17L had a lower alpha helix content and the conjugation of any R3HA ((R)-3-hydroxyhexanoic acid to (R)-3-hydroxydodecanoic acid) to DPI 7L returned the helix content back to levels of DPI 8L. However (R)-3-hydroxyhexanoic did not enhance the anti-cancer activity of DPI 7L and at least 7 carbons were needed in the R3HA to enhance activity of D17L. DP17L needs a longer chain R3HA to achieve the same activity as DP18L conjugated to an R3HA. As a first step to assess the synthetic potential of polyhydroxyalkanoate derived R3HA5, (R)-3-hydroxydecanoic acid was synthetically converted to (+/-)3-chlorodecanoic acid, which when conjugated to DP18L improved its antiproliferative activity against MiaPaCa cells.",
publisher = "Elsevier Science Bv, Amsterdam",
journal = "Journal of Biotechnology",
title = "The chain length of biologically produced (R)-3-hydroxyalkanoic acid affects biological activity and structure of anti-cancer peptides",
pages = "12-7",
volume = "204",
doi = "10.1016/j.jbiotec.2015.02.036"
}

Szwej, E., Devocelle, M., Kenny, S., Guzik, M., O'Connor, S., Nikodinović-Runić, J., Milovanović, J., Maslak, V., Byrne, A. T., Gallagher, W. M., Zulian, Q. R., Zinn, M.,& O'Connor, K.. (2015). The chain length of biologically produced (R)-3-hydroxyalkanoic acid affects biological activity and structure of anti-cancer peptides. in Journal of Biotechnology
Elsevier Science Bv, Amsterdam., 204, 7-12.
https://doi.org/10.1016/j.jbiotec.2015.02.036

Szwej E, Devocelle M, Kenny S, Guzik M, O'Connor S, Nikodinović-Runić J, Milovanović J, Maslak V, Byrne AT, Gallagher WM, Zulian QR, Zinn M, O'Connor K. The chain length of biologically produced (R)-3-hydroxyalkanoic acid affects biological activity and structure of anti-cancer peptides. in Journal of Biotechnology. 2015;204:7-12.
doi:10.1016/j.jbiotec.2015.02.036 .

Szwej, Emilia, Devocelle, Marc, Kenny, Shane, Guzik, Maciej, O'Connor, Stephen, Nikodinović-Runić, Jasmina, Milovanović, Jelena, Maslak, Veselin, Byrne, Annete T., Gallagher, William M., Zulian, Qun Ren, Zinn, Manfred, O'Connor, Kevin , "The chain length of biologically produced (R)-3-hydroxyalkanoic acid affects biological activity and structure of anti-cancer peptides" in Journal of Biotechnology, 204 (2015):7-12,
https://doi.org/10.1016/j.jbiotec.2015.02.036 . .