Strategies to Fabricate Polypeptide-Based Structures via Ring-Opening Polymerization of N-Carboxyanhydrides

Abstract

Abstract:In this review, we provide a general and clear overview about the different alternatives reported to fabricate a myriad of polypeptide architectures based on the ring-opening polymerization of N-carbonyanhydrides (ROP NCAs). First of all, the strategies for the preparation of NCA monomers directly from natural occurring or from modified amino acids are analyzed. The synthetic alternatives to prepare non-functionalized and functionalized NCAs are presented. Protection/deprotection protocols, as well as other functionalization chemistries are discussed in this section. Later on, the mechanisms involved in the ROP NCA polymerization, as well as the strategies developed to reduce the eventually occurring side reactions are presented. Finally, a general overview of the synthetic strategies described in the literature to fabricate different polypeptide architectures is provided. This part of the review is organized depending on the complexity of the macromolecular topology prepared. Therefore, linear homopolypeptides, random and block copolypeptides are described first. The next sections include cyclic and branched polymers such as star polypeptides, polymer brushes and highly branched structures including arborescent or dendrigraft structures.

Accelerated Polypeptide Synthesis via N‐Carboxyanhydride Ring Opening Polymerization in Continuous Flow

“…The synthesis of more complex polypeptide structures (e.g., star shaped polypeptides)useful for applications such as drug delivery or antimicrobial agents [35,36] -is also limited with the AMM choice since these structures often necessitate a multifunctional initiator molecule or terminal reactive handles to direct the formation of complex architecture. [37][38][39] In this regard the NAM pathway offers more opportunities for functionalization, in addition to also enabling the synthesis of polypeptoids if desired.…”

Molecular bionics – engineering biomaterials at the molecular level using biological principles

“…When used in conjunction with solid-phase synthesis, these convergent strategies can allow for total chemical synthesis of much longer proteins and polypeptides (up to ~300 aminoacids). However, these strategies still remain fairly limited for producing polypeptides due to both cost and but the synthetic efforts required (e.g., need for specific orthogonal reactions) which might favour the usage of other synthetic approaches [239,240].…”

Amphiphilic Nucleobase-Containing Polypeptide Copolymers—Synthesis and Self-Assembly

“…Amphiphilic block copolymers are known to self-assemble in aqueous solutions into a wide range of nanostructures including worm-like or spherical micelles and vesicles [ 1 , 2 , 3 ]. In this field, polypeptide-based copolymers show considerable promise as building blocks to design bioinspired nanomaterials interfacing living systems [ 4 , 5 ]. Compared to other synthetic copolymers, those made of amino acids may offer several attractive features, including (1) adoption of ordered secondary conformations (α-helices, β-sheets…) as in natural proteins; (2) improvement of chemical and enzymatic degradability in a biological medium; and (3) providing tailorable and metabolizable building units/blocks [ 6 , 7 ].…”