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dc.contributor.authorKafka, Alexandra
dc.contributor.authorKleffmann, Torsten
dc.contributor.authorRades, Thomas
dc.contributor.authorMcDowell, Arlene
dc.date.available2021-09-13T20:37:40Z
dc.date.copyright2010
dc.identifier.citationKafka AP, Kleffmann T, Rades T, McDowell A. Characterization of Peptide Polymer Interactions in Poly(alkylcyanoacrylate) Nanoparticles: A Mass Spectrometric Approach. Curr Drug Deliv. 2010 Jul;7(3):208-15. PMID: 20497104en_NZ
dc.identifier.urihttp://hdl.handle.net/10523/12262
dc.description.abstractDrug/polymer interactions occur during in situ polymerization of poly(alkylcyanoacrylate) (PACA) formulations. We have used MALDI ionization coupled tandem time-of-flight (TOF) mass spectrometry as an accurate method to characterize covalent peptide/polymer interactions of PACA nanoparticles with the bioactives D-Lys6-GnRH, insulin, [Asn1-Val5]-angiotensin II, and fragments of insulin-like growth factor 1 (IGF-1 (1-3)) and human adrenocorticotropic hormone (h-ACTH, (18-39)) at the molecular level. Covalent interactions forming peptide/PACA co-polymers were identified for D-Lys6-GnRH, [Asn1- Val5]-angiotensin II and IGF-1 (1-3). D-Lys6-GnRH and [Asn1-Val5]-angiotensin II were modified at their histidine side chain within the peptide, whilst IGF-1 (1-3) was modified at the C-terminal glutamic acid residue. The more complex protein insulin did not co-polymerize despite the presence of 2 histidine residues. This might be explained by the engagement of histidine residues in the folding and sterical arrangement of insulin under polymerization conditions. As expected, h-ACTH (18-39) that does not contain histidine residues did not co- polymerize. Lowering the pH did not prevent the co-polymerization of PACA with D-Lys6- GnRH or IGF-1 (1-3). Conclusively, protein and peptide bioactives are potentially reactive towards PACA nanoparticles via various mechanisms with limited interference of pH. Histidines and C-terminal glutamic acid residues have been identified as potential sites of interaction. The likelihood of their engagement in co-polymerization, however, seems dependant on their sterical availability. The potential for co-polymerization should be considered when designing a PACA delivery system for protein and peptide biopharmaceuticals.en_NZ
dc.format.mimetypeapplication/pdf
dc.language.isoenen_NZ
dc.publisherBentham Science Publishersen_NZ
dc.relation.ispartofCurrent Drug Deliveryen_NZ
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectMALDI TOF/TOFen_NZ
dc.subjectco-polmerizationen_NZ
dc.subjectPACAen_NZ
dc.subjectinsulinen_NZ
dc.subjectIGF-1en_NZ
dc.subjectGnRHen_NZ
dc.subjectangiotensinen_NZ
dc.subjecth-ACTHen_NZ
dc.titleCharacterization of Peptide Polymer Interactions in Poly(alkylcyanoacrylate) Nanoparticles: A Mass Spectrometric Approachen_NZ
dc.typeJournal Articleen_NZ
dc.date.updated2021-09-13T07:09:14Z
otago.schoolSchool of Pharmacyen_NZ
otago.relation.issue3en_NZ
otago.relation.volume7en_NZ
otago.bitstream.endpage215en_NZ
otago.bitstream.startpage208en_NZ
otago.openaccessOpen
dc.rights.statementThis version in OUR Archive is the author’s manuscript accepted for publication after peer-review. The published version is: Kafka AP, Kleffmann T, Rades T, McDowell A. Characterization of Peptide Polymer Interactions in Poly(alkylcyanoacrylate) Nanoparticles: A Mass Spectrometric Approach. Curr Drug Deliv. 2010 Jul;7(3):208-15. PMID: 20497104en_NZ
dc.description.refereedPeer Revieweden_NZ
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Attribution-NonCommercial-NoDerivatives 4.0 International
Except where otherwise noted, this item's licence is described as Attribution-NonCommercial-NoDerivatives 4.0 International