Polypeptoids: A perfect match for molecular definition and macromolecular engineering?

Abstract

Precision synthesis of polymers has been a hot topic in recent years. While this is notoriously difficult to address for polymers with a CAC backbone, Merrifield has discovered a way many decades ago for polypeptides. Using a similar approach, N-substituted polypeptides, so-called polypeptoids have been synthesized and studied for about 20 years. In contrast, the living ring-opening polymerization (ROP) of N-substituted N-carboxyanhydrides was among the first living polymerizations to be discovered. More recently, a surge in new synthetic approaches led to the efficient synthesis of cyclic or linear multiblock copolypeptoids. Thus, polypeptoids can be synthesized either by solid phase synthesis to yield complex and exactly defined oligo-and small polymers or by ROP of appropriately N-substituted N-carboxyanhydrides (NNCA) to give linear, cyclic, or star-like polymers. Together with an excellent biocompatibility, this polymer family may have a bright future ahead as biomaterials.

Peptide-Based Polymer Therapeutics

“…It has to be emphasised that there is a growing effort to better understand the structure-activity relationships in order to better define safety and efficacy of these novel therapeutics [15]. At this point, it is worthy to remark an emerging class of pseudo-peptidic polymers: the polypeptoids [39,40]. Basically, these non-natural biomimetic oligomers present an N-substituted glycine backbone which, opposite to polypeptides, is achiral and the side-chain position differs.…”

Peptoids for biomaterials science

“…( Figure 1C). [21][22][23] The polymer of sarcosine, which is the analog of alanine and the simplest peptoid, was actually known from early investigations into living polymerization. 21 The list of peptoid monomers available to NCA polymerization has been significantly expanded in recent years.…”

“…[21][22][23] The polymer of sarcosine, which is the analog of alanine and the simplest peptoid, was actually known from early investigations into living polymerization. 21 The list of peptoid monomers available to NCA polymerization has been significantly expanded in recent years. 21,22 The biorecognition abilities of peptoids have been demonstrated through two decades of peptoid therapeutics research, protein-binding sequence discovery, and secondary structure design, which have been recently reviewed elsewhere.…”

“…21 The list of peptoid monomers available to NCA polymerization has been significantly expanded in recent years. 21,22 The biorecognition abilities of peptoids have been demonstrated through two decades of peptoid therapeutics research, protein-binding sequence discovery, and secondary structure design, which have been recently reviewed elsewhere. 10,15,[24][25][26][27] As originally envisioned, 7 many bioactive sequences have been discovered by screening peptoid libraries.…”

Polypeptoid polymers: Synthesis, characterization, and properties

“…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 chapter is not meant to give a comprehensive review of the research activities in the field. It will focus on the recent development in the synthetic methods to access polypeptoid polymers with well-defined structures and highlight some of the fundamental physicochemical and biological…”