Cell-surface thiols affect cell entry of disulfide-conjugated peptides

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TitreCell-surface thiols affect cell entry of disulfide-conjugated peptides
Type de publicationJournal Article
Nouvelles publications2009
AuteursAubry, S, Burlina F, Dupont E, Delaroche D, Joliot A, Lavielle S, Chassaing G, Sagan S
JournalFaseb Journal
Volume23
Fascicule9
Pagination2956-2967
Année de publicationSep
Numéro0892-6638
Accession NumberISI:000270241000018
Résumé

Cell-penetrating peptides (CPPs) can cross the cell membrane and are widely used to deliver bioactive cargoes inside cells. The cargo and the CPP are often conjugated through a disulfide bridge with the common acceptation that this linker is stable in the extracellular biological medium and should not perturb the internalization process. However, with the use of thiol-specific reagents combined with mass spectrometry (as a quantitative method to measure intracellular concentrations of peptides) and confocal microscopy (as a qualitative method to visualize internalized peptides) analyses, we could show that, depending on the peptide sequence, thiol/disulfide exchange reactions could happen at the cell surface. These exchange reactions lead to the reduction of disulfide conjugates. In addition, it was observed that not only disulfide-but also thiol-containing peptides could cross-react with cell-surface thiols. The peptides cross-linked by thiol-containing membrane proteins were either trapped in the membrane or further internalized. Therefore, a new route of cellular uptake was unveiled that is not restricted to CPPs: a protein kinase C peptide inhibitor that is not cell permeant could cross cell membranes when an activated cysteine (with a 3-nitro-2-pyridinesulfenyl moiety) was introduced in its sequence.-Aubry, S., Burlina, F., Dupont, E., Delaroche, D., Joliot, A., Lavielle, S., Chassaing, G., Sagan, S. Cell-surface thiols affect cell entry of disulfide-conjugated peptides. FASEB J. 23, 2956-2967 (2009). www.fasebj.org

URL<Go to ISI>://000270241000018
DOI10.1096/fj.08-127563
Importer un fichierCell-surface thiols affect cell entry of disulfide-conjugated peptides
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