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

Abstract

This review provides a comprehensive overview of the latest advances in the synthesis, architectural design and biomedical applications of polypeptides and their hybrids.

Density Functional Theory Studies on the Synthesis of Poly(α-Amino Acid)s Via the Amine-Mediated Ring Opening Polymerizations of N-Carboxyanhydrides and N-Thiocarboxyanhydrides

“…Poly(α-amino acid)s (PAAs) are promising biomaterials that have been employed in drug delivery, gene engineering, and self-assembly fields in recent years (Deming, 2016;Gangloff et al, 2016;Tao et al, 2018a;Birke et al, 2018). The synthetic process toward PAA includes ring opening polymerization of a cyclic monomer such as α-amino acid N-carboxyanhydrides (NCAs) and N-thiocarboxyanhydrides (NTAs), solid-phase synthesis, and biological methods (Mazo et al, 2020). NCAs were first prepared by Leuchs (Leuchs, 1906) in 1906, and NTAs were first reported by Aubert and Knott (1950).…”

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

“…[ 5,6 ] Polypeptides are commonly synthesized in one of three ways: solid phase peptide synthesis (SPPS), recombinant DNA synthesis, [ 7,8 ] or N ‐carboxyanhydride ring opening polymerization (NCA ROP). [ 9–11 ] Synthetic sequence‐defined polypeptides are often acquired via (automated) SPPS. Mijalis et al.…”

“…[5,6] Polypeptides are commonly synthesized in one of three ways: solid phase peptide synthesis (SPPS), recombinant DNA synthesis, [7,8] or N-carboxyanhydride ring opening polymerization (NCA ROP). [9][10][11] Synthetic sequence-defined polypeptides are often acquired via (automated) SPPS. Mijalis et al sped up this synthetic approach with a revolutionary automated continuous flow-based procedure for peptide synthesis based on SPPS, reporting convenient synthesis of up 1,2-dichloroethane.…”

“…These recent advances in NCA ring opening polymerization provide an exciting variety of options to access polypeptides with increased speed for a plethora of applications. [11,34] The demonstrated wide utility of polypeptides warrants the continued scientific interest in simplifying and streamlining their syntheses, and it is our aim to demonstrate that adoption of flow chemistry techniques can further add to the toolbox of effective synthetic strategies. Flow chemistry offers advantageous properties such as more efficient mixing, high surface area, and the promise for more convenient scalability.…”

Protein-, (Poly)peptide-, and Amino Acid-Based Nanostructures Prepared via Polymerization-Induced Self-Assembly

“…A common strategy employed to improve their biophysical properties involves their functionalization with synthetic polymers for preparation of protein/peptide–polymer conjugates and hybrid nano-assemblies [ 14 , 15 , 16 , 17 ]. Additionally, alternative approaches for the development of advanced protein-inspired nanomaterials encompass either the synthesis of amphiphilic polypeptide- and polypeptoid-based copolymers via ring-opening polymerization (ROP) of α-amino acid N -carboxyanhydrides (NCAs) [ 18 , 19 , 20 ] or the synthesis of amino acid-containing amphiphiles via controlled radical polymerization techniques [ 21 , 22 ], followed by their self-assembly in aqueous media to yield biorelevant nanostructures of varying morphologies. However, until recently, efforts to develop such self-assembled formulations have majorly focused on strenuous, multi-step procedures at low polymer concentrations, which are often poorly reproducible.…”