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Fluorophore labelin...
Fluorophore labeling of a cell-penetrating peptide significantly alters the mode and degree of biomembrane interaction
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- Hedegaard, Sofie Fogh (författare)
- Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark
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- Derbas, Mohammed Sobhi (författare)
- Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark
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- Lind, Tania Kjellerup (författare)
- Malmö universitet,Institutionen för biomedicinsk vetenskap (BMV)
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- Kasimova, Marina Robertnova (författare)
- Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark; Symphogen A/S, Pederstrupvej 93, 2750, Ballerup, Denmark
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- Christensen, Malene Vinther (författare)
- Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Jagtvej 162, 2100, Copenhagen, Denmark
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- Michaelsen, Maria Hotoft (författare)
- Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark
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- Campbell, Richard A. (författare)
- Institut Laue-Langevin, 71 avenue des Martyrs, CS20156, 38042, Grenoble, France
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- Jorgensen, Lene (författare)
- Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark
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- Franzyk, Henrik (författare)
- Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Jagtvej 162, 2100, Copenhagen, Denmark
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- Cárdenas, Marité (författare)
- Malmö universitet,Institutionen för biomedicinsk vetenskap (BMV)
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- Nielsen, Hanne Morck (författare)
- Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark
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(creator_code:org_t)
- 2018-04-20
- 2018
- Engelska.
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 8:1
- Relaterad länk:
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https://doi.org/10.1...
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https://mau.diva-por... (primary) (Raw object)
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https://www.nature.c...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- The demand for highly efficient macromolecular drugs, used in the treatment of many severe diseases, is continuously increasing. However, the hydrophilic character and large molecular size of these drugs significantly limit their ability to permeate across cellular membranes and thus impede the drugs in reaching their target sites in the body. Cell-penetrating peptides (CPP) have gained attention as promising drug excipients, since they can facilitate drug permeation across cell membranes constituting a major biological barrier. Fluorophores are frequently covalently conjugated to CPPs to improve detection, however, the ensuing change in physico-chemical properties of the CPPs may alter their biological properties. With complementary biophysical techniques, we show that the mode of biomembrane interaction may change considerably upon labeling of the CPP penetratin (PEN) with a fluorophore. Fluorophore-PEN conjugates display altered modes of membrane interaction with increased insertion into the core of model cell membranes thereby exerting membrane-thinning effects. This is in contrast to PEN, which localizes along the head groups of the lipid bilayer, without affecting the thickness of the lipid tails. Particularly high membrane disturbance is observed for the two most hydrophobic PEN conjugates; rhodamine B or 1-pyrene butyric acid, as compared to the four other tested fluorophore-PEN conjugates.
Nyckelord
- Multidisciplinary Sciences
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Hedegaard, Sofie ...
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Derbas, Mohammed ...
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Lind, Tania Kjel ...
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Kasimova, Marina ...
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Christensen, Mal ...
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Michaelsen, Mari ...
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Campbell, Richar ...
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Jorgensen, Lene
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Franzyk, Henrik
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Cárdenas, Marité
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Nielsen, Hanne M ...
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Malmö universitet