An Inspection into Multifarious Ways to Synthesize Poly(Amino Acid)s

Abstract

Poly(𝜶-amino acid)s (PAAs) attract growing attention due to their essential role in the application as biomaterials. To synthesize PAAs with desired structures and properties, scientists have developed various synthetic techniques with respective advantages. Here, different approaches to preparing PAAs are inspected. Basic features and recent progresses of these methods are summarized, including polymerizations of amino acid N-carboxyanhydrides (NCAs), amino acid N-thiocarboxyanhydrides (NTAs), and N-phenoxycarbonyl amino acids (NPCs), as well as other synthetic routes. NCA is the most classical monomer to prepare PAAs with high molecular weights (MWs). NTA polymerizations are promising alternative pathways to produce PAAs, which can tolerate nucleophiles including alcohols, mercaptans, carboxyl acids, and water. By various techniques including choosing appropriate solvents or using organic acids as promoters, NTAs polymerize to produce polypeptoids and polypeptides with narrow dispersities and designed MWs up to 55.0 and 57.0 kg mol −1 , respectively. NPC polymerizations are phosgene-free ways to synthesize polypeptides and polypeptoids. For the future prospects, detail investigations into polymerization mechanisms of NTA and NPC are expected. The synthesis of PAAs with designed topologies and assembly structures is another intriguing topic. The advantages and unsettled problems in various synthetic ways are discussed for readers to choose appropriate approaches for PAAs.

Stealth-like polysarcosine-modified nanoparticles with low dye doses and long blood circulation for efficient breast cancer pulmonary metastasis imaging

“…1a, using our previously synthesized NIR-II small molecule TQF–NH 2 as the initiator, 43 a PSar-modified polymer (TQF–PSar) was successfully obtained with four dense and hydrophilic brush arms by ring-opening polymerization of sarcosine- N -thiocarboxyanhydride (Sar-NTA). 44–47 The 1 H-NMR spectrum demonstrated successful polymerization of PSar (Fig. S1†).…”

Self‐Assembly of Poly(Amino Acid)s Mediated by Secondary Conformations

“…[32,33,34] Among them, poly(amino acid)s (PAAs) have received widespread attention due to their simple and controllable synthesis, good biocompatibility and nontoxic metabolized products, flexible and adjustable functions, as well as the ability to fold into stable secondary structures. [35,36] Additionally, with the development of N-carboxyanhydrides (NCA) ring-opening polymerization (ROP) technology, [37,38] significant progress has been made in the regulation of secondary conformations of PAAs in recent years. [16,30] PAAs have been extensively studied as structural or functional materials such as nanoparticles, nanotubes, and hydrogels.…”

Biodegradable Polysarcosine with Inserted Alanine Residues: Synthesis and Enzymolysis

“…Nowadays, the ring-opening polymerization (ROP) of α-amino acid N -thiocarboxyanhydrides (NTAs) becomes a fashionable way to synthesize tailored polypeptides or polypeptoids with a high MW. Although Kricheldorf et al found NTA and N-substituted NTA (NNTA) were not promising to synthesize high MW polypeptides and polypeptoids because of precipitation of polymers during polymerization and stabilization of thiocarbonate group by solvation, respectively, there have been many efforts paving the way for well-controlled ROP of NTA monomers. ,− Acetic acid (HAc) catalyzes polymerizations of NTA and NNTA to overturn common sense to the most extent because researchers used to think that HAc would inactivate the amino groups at the polymer chain end and impede propagation. Nevertheless, to the best of our knowledge, the copolymerization of NTAs and NNTAs has not been reported yet.…”