Synthetic polypeptides from the ring-opening polymerization of N-carboxyanhydrides (NCAs) are one of the most important biomaterials. The unique features of these synthetic polypeptides, including their chemical diversity of side chains and their ability to form secondary structures, enable their broad applications in the field of gene delivery, drug delivery, bio-imaging, tissue engineering, and antimicrobials. In this review article, we summarize the recent advances in the design of polypeptide-based supramolecular structures, including complexes with nucleic acids, micelles, vesicles, hybrid nanoparticles, and hydrogels. We also highlight the progress in the chemical design of functional polypeptides, which plays a crucial role to manipulate their assembly behaviours and optimize their biomedical performances. Finally, we conclude the review by discussing the future opportunities in this field, including further studies on the secondary structures and cost-effective synthesis of polypeptide materials.

Synthetic polypeptides: from polymer design to supramolecular assembly and biomedical application

Polymers have become one of the largest and most important materials we use in daily life. Their popularity has stemmed from their wide range of material properties combined with their low cost of ...

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Recent Trends in Catalytic Polymerizations

Polypeptides have attracted considerable attention in recent decades due to their inherent biodegradability and tunable cytocompatibility. Macromolecular design in conjunction with rational monomer composition can direct architecture, self-assembly and chemical behavior, ultimately guiding the choice of appropriate application within the biomedical field. This review focuses on the applications of polypeptides alongside the synthetic advances in the ring opening polymerization of α-amino acid N-carboxyanhydrides achieved in the past five years. Key architectures obtained through NCA ROP or in combination with other polymerization methods are reviewed, as these play an important role in the wide range of applications towards which polypeptides have been applied.

Ring opening polymerization of α-amino acids: advances in synthesis, architecture and applications of polypeptides and their hybrids.

Amino acid-derived stimuli-responsive polymers and their applications

Polypeptides have broad applications and can be prepared via ring-opening polymerization of α-amino acid N-carboxyanhydrides (NCAs). Conventional initiators, such as primary amines, give slow NCA polymerization, which requires multiple days to reach completion and can result in substantial side reactions, especially for very reactive NCAs. Moreover, current NCA polymerizations are very sensitive to moisture and must typically be conducted in a glove box. Here we show that lithium hexamethyldisilazide (LiHMDS) initiates an extremely rapid NCA polymerization process that is completed within minutes or hours and can be conducted in an open vessel. Polypeptides with variable chain length (DP = 20–1294) and narrow molecular weight distribution (Mw/Mn = 1.08–1.28) were readily prepared with this approach. Mechanistic studies support an anionic ring opening polymerization mechanism. This living NCA polymerization method allowed rapid synthesis of polypeptide libraries for high-throughput functional screening. Ring-opening polymerizations of α-amino acid N-carboxyanhydrides to form polypeptides are usually sensitive to moisture, slow and can undergo side reactions. Here the authors use lithium hexamethyldisilazide to initiate α-amino acid N-carboxyanhydride polymerizations that is very fast and can be conducted in an open vessel.

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Lithium hexamethyldisilazide initiated superfast ring opening polymerization of alpha-amino acid N -carboxyanhydrides

Phenyl Trimethylsilyl Sulfide-Mediated Controlled Ring-Opening Polymerization of α-Amino Acid N-Carboxyanhydrides

Tyrosine phosphorylation is an important post-translational modification (PTM) that governs numerous cellular processes. Constructing synthetic phosphotyrosine polypeptides helps expand the horizon of our understanding regarding the fundamental aspects and biological consequences of this PTM. Here, we report the synthesis of a novel monomer, O-diethylphospho l-tyrosine N-carboxyanhydride (pOEt TyrNCA), whose ring-opening polymerization (ROP) mediated by hexamethyldisilazane (HMDS) leads to poly(l-phosphotyrosine) (P(pTyr)) derivatives with controllable molecular weights and narrow molecular-weight distributions. Moreover, P(pTyr)15-b-PEG-b-P(pTyr)15 triblock copolymer (TBP15) undergo sol–gel transition in the presence of alkaline phosphatase. The stiffness of the gel is reinforced by the addition of horseradish peroxidase and hydrogen peroxide. These phosphotyrosine-mimicking polymers are realized for the first time by NCA polymerization and are promising materials for a variety of biological applications.

Jingyu Wang

Papers

Phenyl Trimethylsilyl Sulfide-Mediated Controlled Ring-Opening Polymerization of α-Amino Acid N-Carboxyanhydrides

Controlled Synthesis and Enzyme-Induced Hydrogelation of Poly(l-phosphotyrosine)s via Ring-Opening Polymerization of α-Amino Acid N-Carboxyanhydride