Hydrogen-Bonding-Driven 3D Supramolecular Assembly of Peptidomimetic Zipper

Abstract

Hydrogen-bonding-driven three-dimensional (3D) assembly of a peptidomimetic zipper has been established for the first time by using an α/AApeptide zipper that assembles into a de novo lattice arrangement through two layers of hydrogen-bonded linker-directed interactions. Via a covalently bridged 1D 4-helix, drastic enhancement in stability has been achieved in the formed 3D crystalline supramolecular architecture as evidenced by gas-sorption studies. As the first example of an unnatural peptidic zipper, the dimensional augmentation of the zipper differs from metal-coordinated strategies, and may have general implications for the preparation of peptidic functional materials for a variety of future applications.

Orthogonal Halogen‐Bonding‐Driven 3D Supramolecular Assembly of Right‐Handed Synthetic Helical Peptides

“…Foldamer 1 readily crystallized from CH 3 CN/CH 2 Cl 2 (3:1, v/ v) at room temperature,diffracting with aresolution of 0.9 in space group P4 1 2 1 2. [11] These data further proved the uniqueness of the helical pitch and radius of this class of peptidic foldamer.A no ligomer bearing only methyl sulfonyl side chains (without chlorophenyl side chains, oligomer 2, Figure S1) was also synthesized, but despite many attempts crystals could not be prepared. [11] These data further proved the uniqueness of the helical pitch and radius of this class of peptidic foldamer.A no ligomer bearing only methyl sulfonyl side chains (without chlorophenyl side chains, oligomer 2, Figure S1) was also synthesized, but despite many attempts crystals could not be prepared.…”

“…[5] Natural peptides have been extensively explored to build complex high-ordered assemblies,e specially by using the principles of symmetry, [5a, 6] as well as stable,p orous assemblies that are inspired by the ordered architectures of three-dimensional (3D) protein lattices. [8] Of these,A Apeptides (oligomers of N-acylated, N-aminoethyl amino acids) [9] have been proven capable of forming unique hydrogen-bonding-driven structures,such as aright-handed 4.5 helix resembling a phelix, [10] ap orous 3D supramolecular assembly of ap eptidic zipper, [11] and recently,aleft-handed 4 14 helix, [12] demonstrating the strong intramolecular folding propensity of sulfono-g-AApeptides.However,exploiting these secondary structures and intermolecular interactions for molecular recognition, functional materials,a nd other applications remains rare.I n this work, we report ad en ovo type of supramolecular network taking advantage of both inherent hydrogen bonding and orthogonal intermolecular C À X···p and C À X···X À C halogen bonding interactions. [8] Of these,A Apeptides (oligomers of N-acylated, N-aminoethyl amino acids) [9] have been proven capable of forming unique hydrogen-bonding-driven structures,such as aright-handed 4.5 helix resembling a phelix, [10] ap orous 3D supramolecular assembly of ap eptidic zipper, [11] and recently,aleft-handed 4 14 helix, [12] demonstrating the strong intramolecular folding propensity of sulfono-g-AApeptides.However,exploiting these secondary structures and intermolecular interactions for molecular recognition, functional materials,a nd other applications remains rare.I n this work, we report ad en ovo type of supramolecular network taking advantage of both inherent hydrogen bonding and orthogonal intermolecular C À X···p and C À X···X À C halogen bonding interactions.…”

“…Inspired by highly instructive insights from materials science,b iomolecular recognition, and drug design, [14a] and the recently developed 4 13 -helix [11] that features head-to-tail intermolecular hydrogen bonding and weak interlayer halogen bonding in dimeric zippers and 3D supramolecular polymers,w es et out to investigate the supramolecular networks that are expected to form by strong orthogonal halogen bonding.W eh ypothesized that chlorophenyl, bromophenyl, or iodophenyl groups could be attached at the side chains of 4 13 -helices to propagate orthogonal halogen bonding in order to form new supramolecular topologies.W ep osed that CÀX···p halogen bonding and interhelical non-copular C À X···X À Ch alogen bonding would generally exist between 4 13 -helices and drive 3D supramolecular self-assembly.…”

“…In our first attempt, we prepared the 4 13 -helix [11] foldamer 1 (Figure 1b,a no ligomer of a/l-sulfono-g-AA) containing ac hloro substituent at the para-position of the phenyl rings. Foldamer 1 readily crystallized from CH 3 CN/CH 2 Cl 2 (3:1, v/ v) at room temperature,diffracting with aresolution of 0.9 in space group P4 1 2 1 2.…”

Orthogonal Halogen‐Bonding‐Driven 3D Supramolecular Assembly of Right‐Handed Synthetic Helical Peptides

“…In our first attempt, we prepared the 4 13 ‐helix foldamer 1 (Figure b, an oligomer of α/ l ‐sulfono‐γ‐AA) containing a chloro substituent at the para ‐position of the phenyl rings. Foldamer 1 readily crystallized from CH 3 CN/CH 2 Cl 2 (3:1, v/v) at room temperature, diffracting with a resolution of 0.9 Å in space group P 4 1 2 1 2.…”