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  • Jing, Xiaona (author)

Interaction of Peptidomimetics with Bilayer Membranes : Biophysical Characterization and Cellular Uptake

  • Article/chapterEnglish2012

Publisher, publication year, extent ...

  • 2012-03-07
  • American Chemical Society (ACS),2012
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-172820
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-172820URI
  • https://doi.org/10.1021/la204033uDOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Enzymatically stable cell-penetrating alpha-peptide/beta-peptoid peptidomimetics constitute promising drug delivery vehicles for the transport of therapeutic biomacromolecules across membrane barriers. The aim of the present study was to elucidate the mechanism of peptidomimetic-lipid bilayer interactions. A series of peptidomimetics consisting of alternating cationic and hydrophobic residues displaying variation in length and N-terminal end group were applied to fluid-phase, anionic lipid bilayers, and their interaction was investigated using isothermal titration calorimetry (ITC) and ellipsometry. Titration of lipid vesicles into solutions of peptidomimetics resulted in exothermic adsorption processes, and the interaction of all studied peptidomimetics with anionic lipid membranes was found to be enthalpy-driven. The enthalpy and Gibbs free energy (Delta G) proved more favorable with increasing chain length. However, not all charges contribute equally to the interaction, as evidenced by the charge-normalized Delta G being inversely correlated to the sequence length. Ellipsometry data suggested that the hydrophobic residues also played an important role in the interaction process. Furthermore, Delta G extracted from ellipsometry data showed good agreement with that obtained with ITC. To further elucidate their interaction with biological membranes, quantitative uptake and cellular distribution were studied in proliferating HeLa cells by flow cytometry and confocal microscopy. The cellular uptake of carboxyfluorescein-labeled peptidomimetics showed a similar ranking as that obtained from the adsorbed amount, and binding energy to model membranes demonstrated that the initial interaction with the membrane is of key importance for the cellular uptake.

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Added entries (persons, corporate bodies, meetings, titles ...)

  • Kasimova, Marina R. (author)
  • Simonsen, Anders H. (author)
  • Jorgensen, Lene (author)
  • Malmsten, MartinUppsala universitet,Institutionen för farmaci(Swepub:uu)mamal991 (author)
  • Franzyk, Henrik (author)
  • Foged, Camilla (author)
  • Nielsen, Hanne M. (author)
  • Uppsala universitetInstitutionen för farmaci (creator_code:org_t)

Related titles

  • In:Langmuir: American Chemical Society (ACS)28:11, s. 5167-51750743-74631520-5827

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