Engineering the atomic structure of sequence-defined peptoid polymers and their assemblies

Abstract

Peptoids are a family of sequence-defined, non-natural biomimetic polymers which show excellent properties including good chemical and enzymatic stability and high structural tunability. The solid-phase submonomer synthesis method allows precise control over the identity and sequence of chemically diverse side chains, enabling the atomic engineering of their chemical structures for a variety of applications. This unprecedented level of structural control enables access to atomically defined threedimensional chain conformations and assemblies, facilitating the design and optimization of a variety of nanoscale architectures that can function in biology and materials science. In order to approach the rational design of peptoid materials in a more predictive and precise manner, it is crucial to fully understand how chemical information, in the form of the monomer sequence, encodes their folding and assembly into structurally defined, functional 3D shapes. This perspective focuses on recent studies into the atomic engineering of peptoid nanostructures by examining the impact of sequence variations on their secondary and three-dimensional structures, as well as their functional properties.

Bio-instructive materials on-demand – combinatorial chemistry of peptoids, foldamers, and beyond

“…3,4,6,9,58 Based on various sequence-structure analyses, nowadays, both the rational design and the computer-aided structure prediction of peptoid foldamers is possible. 1,5,115,[130][131][132][133][134]…”

Hierarchical Nanomaterials Assembled from Peptoids and Other Sequence-Defined Synthetic Polymers

“…Over the past decades, peptoids have been reviewed under various topics by the Zuckermann group, e.g., peptoid-based nanosheets, peptoid polymers, and the applications of peptoid-based materials. ,,, In addition, Luxenhofer et al presented a complete picture of peptoid history, synthesis, physicochemical characteristics, and applications in the field of molecular engineering . Herein, we provide a comprehensive overview of the hierarchical nanomaterials assembled from peptoids and other sequence-defined synthetic polymers including β-peptides and γ-AApeptides.…”

Quantifying Polypeptoid Conformational Landscapes through Integrated Experiment and Simulation

“…They can now be routinely synthesized at gram scale, sequence-specifically up to 50 monomers in length in a process that eliminates the need for protection/deprotection procedures common in polypeptide synthesis, allowing access to a wide variety of chemistries . As such, they have been extensively explored for a broad range of applications, including as antifoulants, antimicrobials, − other therapeutics, delivery agents, , sensing applications such as stimuli-responsive materials, binder materials for batteries, crystallization modulators, and programmable self-assembly. − Many of these applications leverage the sequence-specificity of polypeptoids that has been shown to significantly modulate secondary − and self-assembled structures , and therefore function. Thus, advancement of polypeptoid-containing materials and the fundamental design rules that they follow requires elucidation of sequence–structure–function relationships.…”