Polymerization Chaperone for the Controlled, Homogeneous Synthesis of Proline-Based Homo- and Copolypeptides

Area of Science:

• Polymer Chemistry
• Biomaterials Science
• Protein Folding

Background:

• Synthesizing well-defined poly-l-proline (PLP) and collagen-like copolypeptides is challenging due to aggregation and folding issues.
• Existing polymerization methods struggle to control conformation and achieve high fidelity for these specific polypeptides.

Purpose of the Study:

• To introduce a "polymerization chaperone" strategy for controlled synthesis of PLP and collagen-like copolypeptides.
• To investigate the multifunctional role of acetic acid in stabilizing polyproline type II (PPII) helices and catalyzing polymerization.

Main Methods:

• Utilized acetic acid as a stoichiometric "polymerization chaperone" with proline N-carboxyanhydride (Pro-NCA) monomer in dichloromethane.
• Investigated the chaperone's roles in solubilization, helix stabilization, ring-opening polymerization catalysis, and chain end fidelity.
• Performed statistical copolymerization with sarcosine NCA and glycine NCA.

Main Results:

• Achieved controlled synthesis of PLP with predictable degrees of polymerization up to 400 and narrow dispersity (Đ < 1.22).
• Demonstrated high in situ selectivity for trans amide formation (trans ratio 0.89-0.99) during polymerization.
• Successfully synthesized PPII helical copolypeptides via copolymerization, which are difficult to obtain with current methods.

Conclusions:

• The "polymerization chaperone" strategy provides a new paradigm for in situ conformational regulation and polymerization catalysis.
• This approach enables precision synthesis of insoluble homopolypeptides and collagen-like copolypeptides.
• The method offers a pathway to novel biomaterials with controlled structures and properties.