Solid‐phase synthesis of three‐armed star‐shaped peptoids and their hierarchical self‐assembly

Abstract

Due to the branched structure feature and unique properties, a variety of star‐shaped polymers have been designed and synthesized. Despite those advances, solid‐phase synthesis of star‐shaped sequence‐defined synthetic polymers that exhibit hierarchical self‐assembly remains a significant challenge. Hence, we present an effective strategy for the solid‐phase synthesis of three‐armed star‐shaped peptoids, in which ethylenediamine was used as the centric star pivot. Based on the sequence of monomer addition, a series of AA′A′′‐type and ABB′‐type peptoids were synthesized and characterized by UPLC‐MS (ultrahigh performance liquid chromatography‐mass spectrometry). By taking advantage of the easy‐synthesis and large side‐chain diversity, we synthesized star‐shaped peptoids with tunable functions. We further demonstrated the aqueous self‐assembly of some representative peptoids into biomimetic nanomaterials with well‐defined hierarchical structures, such as nanofibers and nanotubes. These results indicate that star‐shaped peptoids offer the potential in self‐assembly of biomimetic nanomaterials with tunable chemistries and functions.

The Diverse World of Foldamers: Endless Possibilities of Self-Assembly

“…Peculiar three-armed star-shaped (TASS) peptoids were synthesized by solid-phase synthesis on a common centric star pivot, by attaching three identical chains (AA’A’’-type) or one hydrophilic (or hydrophobic) and two hydrophobic (or hydrophilic) chains (ABB’-type), as shown in Figure 23 d [ 259 ]. Trifluoroacetates of amphiphilic ABB’-type TASS peptoids were then submitted to self-assembly in aqueous environment by dissolution in a 1:1 water/acetonitrile mixture followed by the slow evaporation of acetonitrile.…”

“…[ 258 ]); ( d ) Chemical structures (hydrophilic chains in cyan and hydrophobic chains in blue; common centric star pivot in black), cartoon representations and AFM images with selected height profiles of hierarchical structures from aqueous self-assembly of TASS peptoids: ABB’-1 (left); ABB’-2 (middle); ABB’-3 (right) (adapted with permission from Ref. [ 259 ]).…”

Peptoid-based hierarchically-structured biomimetic nanomaterials: Synthesis, characterization and applications

“…This subtle structural modification provides peptoids with unique structures and properties in contrast to peptides and proteins, such as high stability against protease digestion, enhanced chemical and thermal stability, and the lack of backbone hydrogen bond donors which simplifies the building of peptoid-peptoid and peptoid-surface interactions exclusively through side-chain chemistry. Because of such advantages, in the last several years, amphiphilic peptoids have been frequently designed and used as sequence-defined building blocks to assemble into biomimetic nanomaterials with various hierarchical structures both on the substrate surfaces and in the solution [1,2,[7][8][9][10][11][12][13][14][15][16][17][18]. To access sequence-defined peptoids, a step-wise "sub-monomer" synthesis approach was developed by Zuckermann et al [19] in 1992.…”

“…To date, several review articles on the synthesis, properties, and applications of peptoids have been published [2,27,28]. Herein, it is not our intention to give a comprehensive overview of the latest research progress in the field of peptoid-based nanomaterials, instead, we will give an overview of some recent achievements in the selfassembly of amphiphilic peptoids into hierarchicallystructured materials, such as nanoribbons [10,13,16], nanomembranes [14,15] and nanotubes [8,9,12], highlighting our fundamental understandings of the peptoid assembly pathway and mechanisms using in situ AFM and AFM-DFS techniques. We believe some views and insights from this review will benefit materials scientists for the future design and development of peptoid-based biomimetic na-nomaterials with desired structures and properties.…”

Stacks of Azobenzene Stars: Self-Assembly Scenario and Stabilising Forces Quantified in Computer Modelling

“…There are several classifications of star-shaped azos: they may differ in (i) the number of arms (three [9,10,[14][15][16][17][18][19][20], four [7,21,22], six [23][24][25], nine [26]), (ii) in their centres (nitrogen [9,19], phosphorus [27], silicon [28] or carbon atoms [21,22], benzene [14,16,20,[29][30][31][32], polycyclic aromatic hydrocarbons [25,33], heterocyclic hydrocarbons [34][35][36][37], some chiral groups [6] or bio-active residues [38]), (iii) in the way azobenzenes are attached to the centre (covalently or noncovalently [39]), (iv) in their conformational rigidity (flexible or rigid), (v) in their overall geometry (quasi-planar or 3D). Both the conformational rigidity and the shape of the star are closely related to the chemical nature of the star core, for instance, the planar conjugated fragment in the absence of any fatty linkers between the centre and the azobenzene arms supports the planarity of the star and its rigidity, and vice versa, long hydrocarbon linkers provokes its conformational flexibility [8,30,31].…”