Simultaneous Stabilization and Multimerization of a Peptide α‐Helix by Stapling Polymerization. Issue 13 (10th May 2016)

• Record Type: Journal Article
• Authors: Lee, Young‐Joo; Han, Sanghun; Lim, Yong‐beom
• Is Part Of: Macromolecular rapid communications. Volume 37:Issue 13(2016)
• Page Start: 1021
• Page End: 1026
• Publication Date: 2016-05-10
• Subjects: α‐helices -- biopolymers -- peptides -- polyacrylamides -- stapling polymerization; Macromolecules -- Periodicals; Polymers -- Periodicals; Chemistry -- Periodicals; 547.705
• DOI: 10.1002/marc.201600179
• Languages: English
• ISSNs: 1022-1336

Abstract

Abstract : Maintaining specific conformations of peptide ligands is crucial for improving the efficacy of biological interactions. Here, a one‐pot polymerization strategy for stabilizing the α‐helical conformation of peptides while simultaneously constructing multimeric ligands is presented. The new method, termed stapling polymerization, uses radical polymerization between acryloylated peptide side chains and vinylic monomers. Studies with model peptides indicate that i, i+7 crosslinking is effective for the helix stabilization, whereas i, i+4 crosslinking is not. The stapling polymerization results in the formation of peptide–polyacrylamide conjugates that include ≈3–16 peptides in a single conjugate. This stapling polymerization provides a simple but powerful methodology to fabricate multimeric α‐helices that can further be developed to modulate multivalent biomacromolecular interactions. Abstract : Stapling polymerization is developed for simultaneous α‐helix stabilization and peptide multimerization. The stabilization effect is most pronounced when the crosslinkable amino acid residues are on the same face of the α‐helix and are located at the i and i+7 positions. This strategy can provide a useful tool for developing multimeric α‐helices that can be used to modulate biomacromolecular interactions.