Details

Autor(en) / Beteiligte

• Brunner, Joël
• Borchard, Gerrit

Titel

Structure-activity relationship of a peptide permeation enhancer

Ist Teil von

• Tissue barriers, 2023-01, Vol.11 (1), p.2060692-2060692

Ort / Verlag

United States: Taylor & Francis

Erscheinungsjahr

2023

Quelle

MEDLINE

Beschreibungen/Notizen

• The pentapeptide L-R5 has previously been shown to transiently increase the permeability of nasal epithelial cell layers in vitro, allowing paracellular transport of molecules of up to 4 kDa. Protein kinase C zeta (PKC ζ), a member of a family of serine/threonine kinases was shown to be involved in tight junction modulation induced by L-R5. We show here that the ability of L-R5 to modulate tight junctions is comparable to other permeability enhancers such as bilobalide, latrunculin A or C 10 . Interaction of the peptide with the target protein occurs via electrostatic interaction, with the presence of positive charges being essential for its functionality. L-R5 is myristoylated to allow quick cell entry and onset of activity. While no epithelial cytotoxicity was detected, the hydrophobic myristoyl rest was shown to cause haemolysis. Taken together, these data show that a structural optimization of L-R5 may be possible, both from a toxicological and an efficacy point of view.