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dc.creatorSzwej, Emilia
dc.creatorDevocelle, Marc
dc.creatorKenny, Shane
dc.creatorGuzik, Maciej
dc.creatorO'Connor, Stephen
dc.creatorNikodinović-Runić, Jasmina
dc.creatorRadivojević, Jelena
dc.creatorMaslak, Veselin
dc.creatorByrne, Annete T.
dc.creatorGallagher, William M.
dc.creatorZulian, Qun Ren
dc.creatorZinn, Manfred
dc.creatorO'Connor, Kevin E.
dc.date.accessioned2018-11-22T00:31:30Z
dc.date.available2018-11-22T00:31:30Z
dc.date.issued2015
dc.identifier.issn0168-1656
dc.identifier.urihttp://cherry.chem.bg.ac.rs/handle/123456789/1712
dc.description.abstractConjugation 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.en
dc.publisherElsevier Science Bv, Amsterdam
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/173048/RS//
dc.relationBioplastech Ltd., Dublin, Ireland [BP2013]
dc.relationHEA Ireland PRTLI IV (Bio) Pharmaceutical and Pharmacological Sciences programme
dc.rightsrestrictedAccess
dc.sourceJournal of Biotechnology
dc.subject(R)-3-hydroxyalkanoic acidsen
dc.subjectCarbon chain lengthen
dc.subjectBioactive peptidesen
dc.subjectAnti canceren
dc.subject3-Chlorodecanoic aciden
dc.titleThe chain length of biologically produced (R)-3-hydroxyalkanoic acid affects biological activity and structure of anti-cancer peptidesen
dc.typearticle
dc.rights.licenseARR
dcterms.abstractНикодиновић-Рунић, Јасмина; Сзwеј, Емилиа; О'Цоннор, Степхен; Зулиан, Qун Рен; Зинн, Манфред; О'Цоннор, Кевин Е.; Кеннy, Схане; Радивојевиц, Јелена; Бyрне, Aннете Т.; Девоцелле, Марц; Гузик, Мациеј; Галлагхер, Wиллиам М.; Маслак, Веселин;
dc.citation.volume204
dc.citation.spage7
dc.citation.epage12
dc.identifier.wos000354400000004
dc.identifier.doi10.1016/j.jbiotec.2015.02.036
dc.citation.other204: 7-12
dc.citation.rankM22
dc.identifier.pmid25820126
dc.description.otherSupplementary material: [http://cherry.chem.bg.ac.rs/handle/123456789/3451]
dc.type.versionpublishedVersionen
dc.identifier.scopus2-s2.0-84927595388
dc.identifier.rcubKon_2858


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