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dc.contributor.authorChan, Yiu-Ngok
dc.contributor.authorAmon, Michael
dc.contributor.authorJ. Marano, Robert
dc.contributor.authorWimmer, Norbert
dc.contributor.authorS. Kearns, Philip
dc.contributor.authorManolios, Nicholas
dc.contributor.authorElizabeth Rakoczy, P.
dc.contributor.authorToth, Istvan
dc.date.accessioned2017-05-03T15:03:57Z
dc.date.available2017-05-03T15:03:57Z
dc.date.issued2007
dc.date.modified2008-05-07T09:13:09Z
dc.identifier.issn09680896
dc.identifier.urihttp://hdl.handle.net/10072/18496
dc.description.abstractAbstract-In search of new oligodeoxynucleotide (ODN) delivery agents, we evaluated novel peptides derived from core peptide HGLRILLLKV-OH (CP). CP is a fragment designed from the T-cell antigen receptor (TCR) a-chain transmembrane sequence. CP was able to enter cells including T-cells and inhibited interleukin-2 (IL-2) production. To examine the e?ect of increased lipophilicity on cellular uptake and activity of CP, a lipoamino acid (2-aminododecanoic acid) was incorporated into peptide CP resulting in 2-aminodecanoyl-CP (LP). The toxicity of CP and LP was assessed by measuring the haemolytic activity. Neither compound caused any haemolysis of red blood cells. We have also compared the biological activities of the CP and LP. Using a T-cell antigen presentation assay, the more lipophilic LP caused greater inhibition of IL-2 production than the parent CP in the antigen stimulated T-cells. The LP also showed increased permeability than CP in the Caco-2 cell assay. We utilised the enhanced cell permeability property of LP in oligodeoxynucleotide ODN1 delivery. Isothermal titration calorimetry (ITC) suggested that CP and LP complex with ODN1 in a 12:1 (CP:ODN1) and 15:1 (LP:ODN1) ratio. These complexes were then transfected into human retinal pigment epithelial cells. The level of transfection was measured by the decreased production of the protein human vascular endothelial growth factor (hVEGF). The results revealed greater transfection e?ciency for both CP and LP (47%, 55% more inhibition) compared to commercially available transfection agent cytofectin GSVTM. These results suggested that the CP and particularly its lipophilic analogue LP have the potential to be used as oligodeoxynucleotide delivery systems.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherPergamon
dc.publisher.placeOxford, England
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom4091
dc.relation.ispartofpageto4097
dc.relation.ispartofissue12
dc.relation.ispartofjournalBioorganic & Medicinal Chemistry
dc.relation.ispartofvolume15
dc.rights.retentionY
dc.subject.fieldofresearchMedicinal and biomolecular chemistry
dc.subject.fieldofresearchOrganic chemistry
dc.subject.fieldofresearchPharmacology and pharmaceutical sciences
dc.subject.fieldofresearchcode3404
dc.subject.fieldofresearchcode3405
dc.subject.fieldofresearchcode3214
dc.titleNovel cationic lipophilic peptides for oligodeoxynucleotide delivery
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.facultyGriffith Health, School of Pharmacy
gro.date.issued2007
gro.hasfulltextNo Full Text
gro.griffith.authorChan, Yiu-Ngok


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