Simultaneous Stabilization and Multimerization of a Peptide α-Helix by Stapling Polymerization.

Area of Science:

• Biochemistry
• Polymer Chemistry
• Bioconjugation

Background:

• Specific peptide conformations, particularly alpha-helices, are vital for effective biological interactions.
• Stabilizing these conformations and creating multimeric structures can enhance ligand efficacy.

Purpose of the Study:

• To develop a one-pot polymerization strategy for stabilizing peptide alpha-helical conformations.
• To simultaneously construct multimeric peptide ligands using this novel method.

Main Methods:

• Introduced 'stapling polymerization,' a radical polymerization process.
• Utilized acryloylated peptide side chains and vinylic monomers for crosslinking.
• Investigated i, i+7 and i, i+4 crosslinking strategies for helix stabilization.

Main Results:

• Demonstrated that i, i+7 crosslinking effectively stabilizes the alpha-helical conformation.
• Showcased the formation of peptide-polyacrylamide conjugates containing approximately 3-16 peptides.
• Confirmed the method's efficiency in creating multimeric alpha-helical structures.

Conclusions:

• Stapling polymerization offers a straightforward yet potent approach to fabricate stabilized multimeric alpha-helices.
• This methodology holds potential for developing advanced ligands to modulate multivalent biomacromolecular interactions.