Switchable Coacervate Formation via Amino Acid Functionalization of Poly(dehydroalanine)

Area of Science:

• Polymer Chemistry
• Biomaterials Science
• Supramolecular Chemistry

Background:

• Previously developed poly(S-alkyl-l-homocysteines) (Xaa-C) form environmentally responsive coacervates.
• Understanding molecular structure's impact on polypeptide coacervate formation is crucial for designing new materials.

Purpose of the Study:

• To synthesize and characterize side-chain amino acid-functionalized poly(S-alkyl-rac-cysteines) (Xaa-rac-C).
• To investigate the coacervate formation properties of Xaa-rac-C compared to Xaa-C.
• To explore the influence of specific amino acid side chains, like methionine, on coacervate stability and responsiveness.

Main Methods:

• Post-polymerization modification of poly(dehydroalanine) (A) to create Xaa-rac-C.
• Reaction of unprotected l-amino acid 2-mercaptoethylamides with the A platform.
• Characterization of coacervate properties, including stability in high ionic strength media and redox-switchable behavior.

Main Results:

• Xaa-rac-C formed coacervates with properties similar to Xaa-C, despite differences in main-chain structure.
• Incorporation of l-methionine into Met-rac-C yielded coacervates with enhanced stability in high ionic strength media.
• The thioether groups in Met-rac-C enabled reversible redox switching of coacervate formation.

Conclusions:

• Side-chain amino acid functionalization of polypeptides is a general strategy to promote coacervation.
• Methionine-containing polypeptides offer a pathway to create robust and stimuli-responsive coacervates.
• These findings advance the design of functional polypeptide-based materials for various applications.