5,10,15,20-Tetrakis(pentafluorophenyl)porphyrin as a Functional Platform for Peptide Stapling and Multicyclisation

Area of Science:

• Chemical synthesis
• Supramolecular chemistry
• Bioconjugation

Background:

• Polyfluorinated aromatic reagents facilitate peptide cyclization via nucleophilic aromatic substitution (S_N Ar).
• Existing methods for peptide cyclization can be limited in scope and applicability.

Purpose of the Study:

• To develop a robust and versatile platform for peptide stapling and multicyclisation.
• To create novel 3D peptide architectures using a porphyrin template.

Main Methods:

• Utilizing 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin as a templating agent.
• Employing nucleophilic aromatic substitution (S_N Ar) for peptide modification.
• Investigating reactions with non-protected peptides containing varying numbers of cysteine residues.

Main Results:

• Demonstrated chemoselective peptide stapling and multicyclisation under peptide-compatible conditions.
• Successfully synthesized bicyclic and multicyclic peptides with up to three loops.
• Created a porphyrin-templated stapled peptide conjugate with skin cell penetrating properties and intrinsic fluorescence.

Conclusions:

• The porphyrin-templated platform offers a versatile approach for constructing complex 3D peptide scaffolds.
• This method allows for modular assembly of peptides, enabling diverse architectural designs.
• The developed conjugates show potential for applications in drug delivery and bioimaging.