Polypeptoid polymers: Synthesis, characterization, and properties

Abstract

Polypeptoids, a class of peptidomimetic polymers, have emerged at the forefront of macromolecular and supramolecular science and engineering as the technological relevance of these polymers continues to be demonstrated. The chemical and structural diversity of polypeptoids have enabled access to and adjustment of a variety of physicochemical and biological properties (eg, solubility, charge characteristics, chain conformation, HLB, thermal processability, degradability, cytotoxicity and immunogenicity). These attributes have made this synthetic polymer platform a potential candidate for various biomedical and biotechnological applications. This review will provide an overview of recent development in synthetic methods to access polypeptoid polymers with well-defined structures and highlight some of the fundamental physicochemical and biological properties of polypeptoids that are pertinent to the future development of functional materials based on polypeptoids. | I N TR ODU C TI ONPolypeptoids composed of N-substituted polyglycine backbones are structural mimics of polypeptides ( Figure 1). Because of N-substitution, polypeptoids lack stereogenic centers and hydrogen bonding interactions along the main chains, in sharp contrast to polypeptides.As a result, the global conformations of polypeptoids are strongly dependent on the N-substituent structures, giving rise to random coils or well-defined secondary structures [eg, polyproline I (PPI) helix [1][2][3][4][5][6] and R-sheets] [7][8][9][10][11][12] that are reminiscent of those of polypeptides. The polypeptoid backbone containing tertiary amide linkages is highly polar and hydrophilic. The physicochemical properties of polypeptoids can be tailored by the N-substituent structures, enabling control over the hydrophilicity and lipophilicity balance (HLB), charge characteristics, [13,14] backbone conformation, [1][2][3][4][5][6][7][8][9][10][11][12] solubility, [15][16][17][18][19][20] thermal and crystallization properties of the polypeptoids. [21][22][23][24] Without extensive hydrogen bonding, polypeptoids are thermally processable similar to conventional thermoplastics, [20][21][22][23][24] whereas polypeptides undergo thermal degradation before they can be melt-processed due to the extensive hydrogen bonding interactions. While polypeptoids exhibited enhanced proteolytic stability relative to peptides, [25,26] they can be oxidatively degraded under conditions that mimic tissue inflammation, [27] suggesting their potential in vivo uses as biodegradable materials.Recent advances in the controlled polymerization methods have enabled access to a suite of structurally well-defined polypeptoids with various N-substituent structures and molecular architectures, setting the stage for the future development of polypeptoid materials for various targeted applications. Several review articles on the synthesis, properties, and application of polypeptoids for biomedical or nonbiomedical uses have been published in recent years. [28][29][30][31][32] As a result, this...

Dual‐responsive pegylated polypeptoids with tunable cloud point temperatures

“…Polypeptoids are a class of structural mimics of polypeptides with polar polyglycine backbones and various side groups attached to nitrogen atoms. The overall hydrophilic and hydrophobic properties of polypeptoids can be controlled by varying the N ‐substituent side chains . A few thermo‐responsive polypeptoids have been successfully prepared and the CPs can be adjusted by different approaches.…”

Design and preparation of organic nanomaterials using self‐assembled peptoids

“…Peptoids have been the focus of multiple reviews, with particular emphasis on their synthesis, physico‐chemical properties, or on a particular class of assembled material . The focus of this review will be on the most relevant advances in the development of peptoid self‐assembled nanostructures, highlighting the versatility of these materials in many applicative fields, such as medicine, catalysis and nanoscience.…”

Linking two worlds in polymer chemistry: The influence of block uniformity and dispersity in amphiphilic block copolypeptoids on their self‐assembly

“…The research field of (poly)peptoids is mainly divided into two camps. On the one hand, uniform molecules are created by step‐wise synthesis on solid supports, and on the other hand, disperse polymers are generated via ring‐opening polymerizations.…”