Anion Recognition as a Supramolecular Switch of Cell Internalization

Area of Science:

• Biochemistry
• Molecular Biology
• Cell Biology

Background:

• Oligoarginine peptides are known for their cell-penetrating properties.
• Targeted delivery of molecules into cells remains a challenge.
• Designed peptides offer potential for controlled cellular uptake.

Purpose of the Study:

• To investigate the cell internalization mechanism of designed oligoarginine peptides.
• To determine the role of a supramolecular host in peptide delivery.
• To assess the independent cell membrane permeability of the peptide and host.

Main Methods:

• Synthesis of oligoarginine peptides with glutamic acid residues and a pyranine tag.
• Preparation of a specific supramolecular host.
• Cell-based assays to monitor peptide and complex internalization.
• Control experiments with individual components.

Main Results:

• Cell internalization of the designed peptide was observed only upon addition of the supramolecular host.
• The host specifically binds to the pyranine moiety of the peptide.
• Neither the peptide nor the host alone could cross the cell membrane.
• The peptide-host complex efficiently traversed the cell membrane.

Conclusions:

• Supramolecular complexation is a viable strategy to trigger and facilitate cell internalization of otherwise impermeable peptides.
• This approach enables targeted delivery of designed peptides into cells.
• The host-guest interaction is crucial for overcoming cell membrane barriers.