Peptide Self-Assembly Controlled Photoligation of Polymers

Area of Science:

• Bioorthogonal Chemistry
• Supramolecular Chemistry
• Polymer Chemistry

Background:

• Bioorthogonal chemistry relies on efficient reactions in water, but the available reactions are limited.
• Conventional methods focus on altering functional group reactivity, whereas this study explores environment-driven efficiency.
• Enzymes provide controlled reaction environments, inspiring a catalyst-free approach using self-assembly.

Purpose of the Study:

• To develop a novel strategy for enhancing inefficient chemical ligations using self-assembled environments.
• To overcome the limitations of [2 + 2] photocycloadditions, such as low efficiency at low concentrations and oxygen sensitivity.
• To create a switchable ligation system controlled by pH-induced self-assembly.

Main Methods:

• Designing peptide sequences encoding beta-sheet structures to self-assemble.
• Integrating hydrophobic photoreactive units and hydrophilic polymers with self-assembling peptides.
• Investigating the effect of pH on self-assembly, morphology, and photocycloaddition efficiency in aqueous solutions.

Main Results:

• Self-assembly of peptide-polymer conjugates into small structures in water enabled highly efficient photoligation (>90% in 2 min at 0.034 mM).
• Protonation at low pH induced a morphological change to 1D fibers, halting the photocycloaddition reaction.
• The photoligation was switchable ON/OFF via pH changes and highly efficient compared to reactions in organic solvents (no reaction in DMF at 0.34 mM).

Conclusions:

• Self-assembly of polymer ligation targets can create localized environments that dramatically enhance reaction efficiency.
• This catalyst-free approach overcomes key limitations of [2 + 2] photocycloadditions, expanding the toolbox for bioorthogonal chemistry.
• The pH-switchable nature of the ligation offers precise control for applications in complex chemical systems.