Structure-activity relationship of a peptide permeation enhancer

Area of Science:

• Biochemistry
• Cell Biology
• Pharmacology

Background:

• The pentapeptide L-R5 transiently increases nasal epithelial cell layer permeability in vitro.
• Protein kinase C zeta (PKC ζ) is implicated in L-R5-induced tight junction modulation.

Purpose of the Study:

• To compare L-R5's tight junction modulation ability with other permeability enhancers.
• To investigate the mechanism of L-R5 interaction with its target protein.
• To assess the toxicological profile of L-R5, particularly the myristoyl group.

Main Methods:

• In vitro permeability assays of nasal epithelial cell layers.
• Comparison with known permeability enhancers (bilobalide, latrunculin A, C10).
• Analysis of L-R5's interaction mechanism via electrostatic interactions.
• Assessment of epithelial cytotoxicity and haemolysis.

Main Results:

• L-R5's tight junction modulation is comparable to bilobalide, latrunculin A, and C10.
• Positive charges on L-R5 are crucial for its functionality.
• Myristoylation facilitates cell entry and activity onset.
• No epithelial cytotoxicity was observed, but the myristoyl group caused haemolysis.

Conclusions:

• L-R5 effectively modulates tight junctions, with potential for structural optimization.
• The myristoyl group's haemolytic activity necessitates modification for improved safety.
• Further research into L-R5's structure-activity and structure-toxicity relationships is warranted.