Hierarchical supramolecular assembly of a single peptoid polymer into a planar nanobrush with two distinct molecular packing motifs.

Hierarchical nanomaterials have received increasing interest for many applications. Here, we report a facile programmable strategy based on an embedded segmental crystallinity design to prepare unprecedented supramolecular planar nanobrush-like structures composed of two distinct molecular packing motifs, by the self-assembly of one particular diblock copolymer poly(ethylene glycol)-block-poly(N-octylglycine) in a one-pot preparation. We demonstrate that the superstructures result from the temperature-controlled hierarchical self-assembly of preformed spherical micelles by optimizing the crystallization-solvophobicity balance. Particularly remarkable is that these micelles first assemble into linear arrays at elevated temperatures, which, upon cooling, subsequently template further lateral, crystallization-driven assembly in a living manner. Addition of the diblock copolymer chains to the growing nanostructure occurs via a loosely organized micellar intermediate state, which undergoes an unfolding transition to the final crystalline state in the nanobrush. This assembly mechanism is distinct from previous crystallization-driven approaches which occur via unimer addition, and is more akin to protein crystallization. Interestingly, nanobrush formation is conserved over a variety of preparation pathways. The precise control ability over the superstructure, combined with the excellent biocompatibility of polypeptoids, offers great potential for nanomaterials inaccessible previously for a broad range of advanced applications.

DNA origami protection and molecular interfacing through engineered sequence-defined peptoids.

DNA nanotechnology has established approaches for designing programmable and precisely controlled nanoscale architectures through specific Watson-Crick base-pairing, molecular plasticity, and intermolecular connectivity. In particular, superior control over DNA origami structures could be beneficial for biomedical applications, including biosensing, in vivo imaging, and drug and gene delivery. However, protecting DNA origami structures in complex biological fluids while preserving their structural characteristics remains a major challenge for enabling these applications. Here, we developed a class of structurally well-defined peptoids to protect DNA origamis in ionic and bioactive conditions and systematically explored the effects of peptoid architecture and sequence dependency on DNA origami stability. The applicability of this approach for drug delivery, bioimaging, and cell targeting was also demonstrated. A series of peptoids (PE1-9) with two types of architectures, termed as "brush" and "block," were built from positively charged monomers and neutral oligo-ethyleneoxy monomers, where certain designs were found to greatly enhance the stability of DNA origami. Through experimental and molecular dynamics studies, we demonstrated the role of sequence-dependent electrostatic interactions of peptoids with the DNA backbone. We showed that octahedral DNA origamis coated with peptoid (PE2) can be used as carriers for anticancer drug and protein, where the peptoid modulated the rate of drug release and prolonged protein stability against proteolytic hydrolysis. Finally, we synthesized two alkyne-modified peptoids (PE8 and PE9), conjugated with fluorophore and antibody, to make stable DNA origamis with imaging and cell-targeting capabilities. Our results demonstrate an approach toward functional and physiologically stable DNA origami for biomedical applications.

Compact Peptoid Molecular Brushes for Nanoparticle Stabilization.

Controlling the interfaces and interactions of colloidal nanoparticles (NPs) via tethered molecular moieties is crucial for NP applications in engineered nanomaterials, optics, catalysis, and nanomedicine. Despite a broad range of molecular types explored, there is a need for a flexible approach to rationally vary the chemistry and structure of these interfacial molecules for controlling NP stability in diverse environments, while maintaining a small size of the NP molecular shell. Here, we demonstrate that low-molecular-weight, bifunctional comb-shaped, and sequence-defined peptoids can effectively stabilize gold NPs (AuNPs). The generality of this robust functionalization strategy was also demonstrated by coating of silver, platinum, and iron oxide NPs with designed peptoids. Each peptoid (PE) is designed with varied arrangements of a multivalent AuNP-binding domain and a solvation domain consisting of oligo-ethylene glycol (EG) branches. Among designs, a peptoid (PE5) with a diblock structure is demonstrated to provide a superior nanocolloidal stability in diverse aqueous solutions while forming a compact shell (∼1.5 nm) on the AuNP surface. We demonstrate by experiments and molecular dynamics simulations that PE5-coated AuNPs (PE5/AuNPs) are stable in select organic solvents owing to the strong PE5 (amine)-Au binding and solubility of the oligo-EG motifs. At the vapor-aqueous interface, we show that PE5/AuNPs remain stable and can self-assemble into ordered 2D lattices. The NP films exhibit strong near-field plasmonic coupling when transferred to solid substrates.

Atomic-level engineering and imaging of polypeptoid crystal lattices.

Rational design of supramolecular nanomaterials fundamentally depends upon an atomic-level understanding of their structure and how it responds to chemical modifications. Here we studied a series of crystalline diblock copolypeptoids by a combination of sequence-controlled synthesis, cryogenic transmission electron microscopy, and molecular dynamics simulation. This family of amphiphilic polypeptoids formed free-floating 2-dimensional monolayer nanosheets, in which individual polymer chains and their relative orientations could be directly observed. Furthermore, bromine atom side-chain substituents in nanosheets were directly visualized by cryogenic transmission electron microscopy, revealing atomic details in position space inaccessible by conventional scattering techniques. While the polypeptoid backbone conformation was conserved across the set of molecules, the nanosheets exhibited different lattice packing geometries dependent on the aromatic side chain para substitutions. Peptoids are inherently achiral, yet we showed that sequences containing an asymmetric aromatic substitution pattern pack with alternating rows adopting opposite backbone chiralities. These atomic-level insights into peptoid nanosheet crystal structure provide guidance for the future design of bioinspired nanomaterials with more precisely controlled structures and properties.

Peptoid nanosheets exhibit a new secondary-structure motif.

A promising route to the synthesis of protein-mimetic materials that are capable of complex functions, such as molecular recognition and catalysis, is provided by sequence-defined peptoid polymers--structural relatives of biologically occurring polypeptides. Peptoids, which are relatively non-toxic and resistant to degradation, can fold into defined structures through a combination of sequence-dependent interactions. However, the range of possible structures that are accessible to peptoids and other biological mimetics is unknown, and our ability to design protein-like architectures from these polymer classes is limited. Here we use molecular-dynamics simulations, together with scattering and microscopy data, to determine the atomic-resolution structure of the recently discovered peptoid nanosheet, an ordered supramolecular assembly that extends macroscopically in only two dimensions. Our simulations show that nanosheets are structurally and dynamically heterogeneous, can be formed only from peptoids of certain lengths, and are potentially porous to water and ions. Moreover, their formation is enabled by the peptoids' adoption of a secondary structure that is not seen in the natural world. This structure, a zigzag pattern that we call a Σ('sigma')-strand, results from the ability of adjacent backbone monomers to adopt opposed rotational states, thereby allowing the backbone to remain linear and untwisted. Linear backbones tiled in a brick-like way form an extended two-dimensional nanostructure, the Σ-sheet. The binary rotational-state motif of the Σ-strand is not seen in regular protein structures, which are usually built from one type of rotational state. We also show that the concept of building regular structures from multiple rotational states can be generalized beyond the peptoid nanosheet system.

Conformations of peptoids in nanosheets result from the interplay of backbone energetics and intermolecular interactions.

The conformations adopted by the molecular constituents of a supramolecular assembly influence its large-scale order. At the same time, the interactions made in assemblies by molecules can influence their conformations. Here we study this interplay in extended flat nanosheets made from nonnatural sequence-specific peptoid polymers. Nanosheets exist because individual polymers can be linear and untwisted, by virtue of polymer backbone elements adopting alternating rotational states whose twists oppose and cancel. Using molecular dynamics and quantum mechanical simulations, together with experimental data, we explore the design space of flat nanostructures built from peptoids. We show that several sets of peptoid backbone conformations are consistent with their being linear, but the specific combination observed in experiment is determined by a combination of backbone energetics and the interactions made within the nanosheet. Our results provide a molecular model of the peptoid nanosheet consistent with all available experimental data and show that its structure results from a combination of intra- and intermolecular interactions.

Minimizing Crinkling of Soft Specimens Using Holey Gold Films on Molybdenum Grids for Cryogenic Electron Microscopy.

We introduce a novel composite holey gold support that prevents cryo-crinkling and reduces beam-induced motion of soft specimens, building on the previously introduced all-gold support. The composite holey gold support for high-resolution cryogenic electron microscopy of soft crystalline membranes was fabricated in two steps. In the first step, a holey gold film was transferred on top of a molybdenum grid. In the second step, a continuous thin carbon film was transferred onto the holey gold film. This support (Au/Mo grid) was used to image crystalline synthetic polymer membranes. The low thermal expansion of Mo is not only expected to avoid cryo-crinkling of the membrane when the grids are cooled to cryogenic temperatures, but it may also act to reduce whatever crinkling existed even before cooling. The Au/Mo grid exhibits excellent performance with specimens tilted to 45°. This is demonstrated by quantifying beam-induced motion and differences in local defocus values. In addition, images of specimens on the Au/Mo grids that are tilted at 45° show high-resolution information of the crystalline membranes that, after lattice-unbending, extends beyond 1.5 Å in the direction perpendicular to the tilt axis.

Mass spectrometry studies of the fragmentation patterns and mechanisms of protonated peptoids.

Peptoids belong to a class of sequence-controlled polymers comprising of N-alkylglycine. This study focuses on using tandem mass spectrometry techniques to characterize the fragmentation patterns of a set of singly and doubly protonated peptoids consisting of one basic residue placed at different positions. The singly protonated peptoids fragment by producing predominately high-abundant C-terminal ions called Y-ions and low-abundant N-terminal ions called B-ions. Computational studies suggest that the proton affinity (PA) of the C-terminal fragments is generally higher than that of the N-terminal fragments, and the PA of the former increases as the fragments are elongated. The B-ions are likely formed upon dissociating the proton-activated amide bonds via an oxazolone structure, and the Y-ions are produced subsequently by abstracting a proton from the newly formed B-ions, which is energetically favored. The doubly protonated peptoids prefer to fragment closest to either the N- or the C-terminus and produce corresponding B/Y-ion pairs. The basic residue seems to dictate the preferred fragmentation site, which may be the result of minimizing the repulsion between the two charges. Water and terminal neutral losses are a facile process accompanying the peptoid fragmentation in both charge states. The patterns appear to be highly influenced by the location of the basic residue.

Lipid-anchor display on peptoid nanosheets via co-assembly for multivalent pathogen recognition.

Biological systems have evolved sophisticated molecular assemblies capable of exquisite molecular recognition across length scales ranging from angstroms to microns. For instance, the self-organization of glycolipids and glycoproteins on cell membranes allows for molecular recognition of a diversity of ligands ranging from small molecules and proteins to viruses and whole cells. A distinguishing feature of these 2D surfaces is they achieve exceptional binding selectivity and avidity by exploiting multivalent binding interactions. Here we develop a 2D ligand display platform based on peptoid nanosheets that mimics the structure and function of the cell membrane. A variety of small-molecule lipid-conjugates were co-assembled with the peptoid chains to create a diversity of functionalized nanosheet bilayers with varying display densities. The functional heads of the lipids were shown to be surface-exposed, and the carbon tails immobilized into the hydrophobic interior. We demonstrate that saccharide-functionalized nanosheets (e.g., made from globotriaosylsphingosine or 1,2-dipalmitoyl-sn-glycero-3-phospho((ethyl-1',2',3'-triazole)triethyleneglycolmannose)) can have very diverse binding properties, exhibiting specific binding to multivalent proteins as well as to intact bacterial cells. Analysis of sugar display densities revealed that Shiga toxin 1 subunit B (a pentameric protein) and FimH-expressing Escherichia coli (E. coli) bind through the cooperative binding behavior of multiple carbohydrates. The ability to readily incorporate and display a wide variety of lipidated cargo on the surface of peptoid nanosheets makes this a convenient route to soluble, cell-surface mimetic materials. These materials hold great promise for drug screening, biosensing, bioremediation, and as a means to combat pathogens by direct physical binding through a well-defined, multivalent 2D material.

Foldamer hypothesis for the growth and sequence differentiation of prebiotic polymers.

It is not known how life originated. It is thought that prebiotic processes were able to synthesize short random polymers. However, then, how do short-chain molecules spontaneously grow longer? Also, how would random chains grow more informational and become autocatalytic (i.e., increasing their own concentrations)? We study the folding and binding of random sequences of hydrophobic ([Formula: see text]) and polar ([Formula: see text]) monomers in a computational model. We find that even short hydrophobic polar (HP) chains can collapse into relatively compact structures, exposing hydrophobic surfaces. In this way, they act as primitive versions of today's protein catalysts, elongating other such HP polymers as ribosomes would now do. Such foldamer catalysts are shown to form an autocatalytic set, through which short chains grow into longer chains that have particular sequences. An attractive feature of this model is that it does not overconverge to a single solution; it gives ensembles that could further evolve under selection. This mechanism describes how specific sequences and conformations could contribute to the chemistry-to-biology (CTB) transition.

Electrostatic Assemblies of Single-Walled Carbon Nanotubes and Sequence-Tunable Peptoid Polymers Detect a Lectin Protein and Its Target Sugars.

A primary limitation to real-time imaging of metabolites and proteins has been the selective detection of biomolecules that have no naturally occurring or stable molecular recognition counterparts. We present developments in the design of synthetic near-infrared fluorescent nanosensors based on the fluorescence modulation of single-walled carbon nanotubes (SWNTs) with select sequences of surface-adsorbed N-substituted glycine peptoid polymers. We assess the stability of the peptoid-SWNT nanosensor candidates under variable ionic strengths, protease exposure, and cell culture media conditions and find that the stability of peptoid-SWNTs depends on the composition and length of the peptoid polymer. From our library, we identify a peptoid-SWNT assembly that can detect lectin protein wheat germ agglutinin (WGA) with a sensitivity comparable to the concentration of serum proteins. To demonstrate the retention of nanosensor-bound protein activity, we show that WGA on the nanosensor produces an additional fluorescent signal modulation upon exposure to the lectin's target sugars, suggesting the lectin protein remains active and selectively binds its target sugars through ternary molecular recognition interactions relayed to the nanosensor. Our results inform design considerations for developing synthetic molecular recognition elements by assembling peptoid polymers on SWNTs and also demonstrate these assemblies can serve as optical nanosensors for lectin proteins and their target sugars. Together, these data suggest certain peptoid sequences can be assembled with SWNTs to serve as versatile optical probes to detect proteins and their molecular substrates.

Cooperative Intramolecular Hydrogen Bonding Strongly Enforces cis-Peptoid Folding.

Sequence-defined peptoids, or N-substituted glycines, are an attractive class of bioispired polymer due to their biostability and efficient synthesis. However, the de novo design of folded peptoids with precise three-dimensional structures has been hindered by limited means to deterministically control backbone conformation. Peptoid folds are generally destabilized by the cis/trans backbone-amide isomerization, and few side-chains are capable of enforcing a specific amide conformation. Here, we show that a novel class of cationic alkyl ammonium ethyl side-chains demonstrates significant enforcement of the cis-amide backbone (Kcis/trans up to 70) using an unexpected ensemble of weak intramolecular CH-O and/or NH-O hydrogen bonds between the side-chain and the backbone carbonyl moieties. These interactions are evidenced by X-ray crystallography, variable-temperature NMR spectroscopy, and DFT calculations. Moreover, these side-chains are inexpensive, structurally diverse, hydrophilic, and can be integrated into longer peptoid sequences via solid-phase synthesis. Notably, we extended these concepts to synthesize a water-soluble peptoid 10-mer that adopts one predominant fold in solution, as determined by multidimensional NMR spectroscopy. This decamer, to the best of our knowledge, is the longest linear peptoid sequence atomically characterized to retain a well-folded structure. These findings fill a critical gap in peptoid folding and should propel the development of peptoid applications in a broad range of contexts, from pharmaceutical to material sciences.

Phosphoramitoids-A submonomer approach to sequence defined N-substituted phosphoramidate polymers.

There is a growing interest in new methods to generate bio-inspired, chemically diverse, sequence-defined synthetic polymers. Solid-phase submonomer approaches offer facile access to these types of materials, since they take advantage of readily available synthons. Submonomer approaches to date have been applied to peptidomimetics with oligo-amide backbones. Here we extend the approach to a phosphorous-containing backbone, where N-substituted phosphoramidate oligomers are constructed from a set of amine submonomers, diphenyl H-phosphonate, and cyclohexane diol. The key chemical steps in chain elongation are a chain extension reaction based on H-phosphonate (P III) chemistry, and a side chain attachment step based on the Atherton-Todd reaction. Cheap, stable chemical reagents are used without heating, all reaction times are 30 minutes or less and open to air, and no main-chain protecting groups are required. Phosphoramitoid tetramers and pentamers displaying a variety of side chain functionalities were synthesized by a three-step solid-phase submonomer method, typically with >85% crude purities.

Stereochemistry of polypeptoid chain configurations.

Like polypeptides, peptoids, or N-substituted glycine oligomers, have intrinsic conformational preferences due to their amide backbones and close spacing of side chain substituents. However, the conformations that peptoids adopt are distinct from polypeptides due to several structural differences: the peptoid backbone is composed of tertiary amide bonds that have trans and cis conformers similar in energy, they lack a backbone hydrogen bond donor, and have an N-substituent. To better understand how these differences manifest in actual peptoid structures, we analyzed 46 high quality, experimentally determined peptoid structures reported in the literature to extract their backbone conformational preferences. One hundred thirty-two monomer dihedral angle pairs were compared to the calculated energy landscape for the peptoid Ramachandran plot, and were found to fall within the expected minima. Interestingly, only two regions of the backbone dihedral angles ϕ and ψ were found to be populated that are mirror images of each other. Furthermore, these two conformers are present in both cis and trans forms. Thus, there are four primary conformers that are sufficient to describe almost all known backbone conformations for peptoid oligomers, despite conformational constraints imposed by a variety of side chains, macrocyclization, or crystal packing forces. Because these conformers are predominant in peptoid structure, and are distinct from those found in protein secondary structures, we propose a simple naming system to aid in the description and classification of peptoid structure.

Unconstrained peptoid tetramer exhibits a predominant conformation in aqueous solution.

Conformational control in peptoids, N-substituted glycines, is crucial for the design and synthesis of biologically-active compounds and atomically-defined nanomaterials. While there are a growing number of structural studies in solution, most have been performed with conformationally-constrained short sequences (e.g., sterically-hindered sidechains or macrocyclization). Thus, the inherent degree of heterogeneity of unconstrained peptoids in solution remains largely unstudied. Here, we explored the folding landscape of a series of simple peptoid tetramers in aqueous solution by NMR spectroscopy. By incorporating specific 13 C-probes into the backbone using bromoacetic acid-2-13 C as a submonomer, we developed a new technique for sequential backbone assignment of peptoids based on the 1,n-Adequate pulse sequence. Unexpectedly, two of the tetramers, containing an N-(2-aminoethyl)glycine residue (Nae), had preferred conformations. NMR and molecular dynamics studies on one of the tetramers showed that the preferred conformer (52%) had a trans-cis-trans configuration about the three amide bonds. Moreover, >80% of the ensemble contained a cis amide bond at the central amide. The backbone dihedral angles observed fall directly within the expected minima in the peptoid Ramachandran plot. Analysis of this compound against similar peptoid analogs suggests that the commonly used Nae monomer plays a key role in the stabilization of peptoid structure via a side-chain-to-main-chain interaction. This discovery may offer a simple, synthetically high-yielding approach to control peptoid structure, and suggests that peptoids have strong intrinsic conformational preferences in solution. These findings should facilitate the predictive design of folded peptoid structures, and accelerate application in areas ranging from drug discovery to biomimetic nanoscience.

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

The self-assembly of block copolymers has captured the interest of scientists for many decades because it can induce ordered structures and help to imitate complex structures found in nature. In contrast to proteins, nature's most functional hierarchical structures, conventional polymers are disperse in their length distribution. Here, we synthesized hydrophilic and hydrophobic polypeptoids via solid-phase synthesis (uniform) and ring-opening polymerization (disperse). Differential scanning calorimetry measurements showed that the uniform hydrophobic peptoids converge to a maximum of the melting temperature at a much lower chain length than their disperse analogs, showing that not only the chain length but also the dispersity has a considerable impact on the thermal properties of those homopolymers. These homopolymers were then coupled to yield amphiphilic block copolypeptoids. SAXS and AFM measurements confirm that the dispersity plays a major role in microphase separation of these macromolecules, and it appears that uniform hydrophobic blocks form more ordered structures.

Uniform, Large-Area, Highly Ordered Peptoid Monolayer and Bilayer Films for Sensing Applications.

The production of atomically defined, uniform, large-area 2D materials remains as a challenge in materials chemistry. Many methods to produce 2D nanomaterials suffer from limited lateral film dimensions, lack of film uniformity, or limited chemical diversity. These issues have hindered the application of these materials to sensing applications, which require large-area uniform films to achieve reliable and consistent signals. Furthermore, the development of a 2D material system that is biocompatible and readily chemically tunable has been a fundamental challenge. Here, we report a simple, robust method for the production of large-area, uniform, and highly tunable monolayer and bilayer films, from sequence-defined peptoid polymers, and their application as highly selective molecular recognition elements in sensor production. Monolayers and bilayer films were produced on the centimeter scale using Langmuir-Blodgett methods and exhibited a high degree of uniformity and ordering as evidenced by atomic force microscopy, electron diffraction, and grazing incidence X-ray scattering. We further demonstrated the utility of these films in sensing applications by employing the biolayer interferometry technique to detect the specific binding of the pathogen derived proteins, shiga toxin and anthrax protective antigen, to peptoid-coated sensors.

Effect of processing and end groups on the crystal structure of polypeptoids studied by cryogenic electron microscopy at atomic length scales.

Cryogenic electron microscopy at atomic length scales was used to study the structure of self-assembled crystalline nanosheets obtained from a series of polypeptoids with the same chain architecture but with different end groups. While long-range order is enhanced by slowing down the self-assembly process, the dominant crystalline motif was found to be a sensitive function of both processing details and end group chemistry. In some cases, adjacent rows of polypeptoid molecules adopt anti-parallel V-shaped side chain conformations. In other cases, adjacent rows of polypeptoid molecules adopt parallel V-shaped side chain conformations. Interestingly, the unit cell is rectangular in both cases with dimensions a = 4.5 Å and c = 50 Å. In all cases, long-range order, quantified by the average number of concatenated unit cells of the same type, is more prevalent along the a direction.

Self-assembly of crystalline nanotubes from monodisperse amphiphilic diblock copolypeptoid tiles.

The folding and assembly of sequence-defined polymers into precisely ordered nanostructures promises a class of well-defined biomimetic architectures with specific function. Amphiphilic diblock copolymers are known to self-assemble in water to form a variety of nanostructured morphologies including spheres, disks, cylinders, and vesicles. In all of these cases, the predominant driving force for assembly is the formation of a hydrophobic core that excludes water, whereas the hydrophilic blocks are solvated and extend into the aqueous phase. However, such polymer systems typically have broad molar mass distributions and lack the purity and sequence-defined structure often associated with biologically derived polymers. Here, we demonstrate that purified, monodisperse amphiphilic diblock copolypeptoids, with chemically distinct domains that are congruent in size and shape, can behave like molecular tile units that spontaneously assemble into hollow, crystalline nanotubes in water. The nanotubes consist of stacked, porous crystalline rings, and are held together primarily by side-chain van der Waals interactions. The peptoid nanotubes form without a central hydrophobic core, chirality, a hydrogen bond network, and electrostatic or π-π interactions. These results demonstrate the remarkable structure-directing influence of n-alkane and ethyleneoxy side chains in polymer self-assembly. More broadly, this work suggests that flexible, low-molecular-weight sequence-defined polymers can serve as molecular tile units that can assemble into precision supramolecular architectures.

Universal Relationship between Molecular Structure and Crystal Structure in Peptoid Polymers and Prevalence of the cis Backbone Conformation.

Peptoid polymers are often crystalline in the solid-state as examined by X-ray scattering, but thus far, there has been no attempt to identify a common structural motif among them. In order to probe the relationship between molecular structure and crystal structure, we synthesized and analyzed a series of crystalline peptoid copolymers, systematically varying peptoid side-chain length (S) and main-chain length (N). We also examined X-ray scattering data from 18 previously reported peptoid polymers. In all peptoids, we found that the unit cell dimensions, a, b, and c, are simple functions of S and N: a (Å) = 4.55, b (Å) = [2.98]N + 0.35, and c (Å) = [1.86]S + 5.5. These relationships, which apply to both bulk crystals and self-assembled nanosheets in water, indicate that the molecules adopt extended, planar conformations. Furthermore, we performed molecular dynamics simulations (MD) of peptoid polymer lattices, which indicate that all backbone amides adopt the cis conformation. This is a surprising conclusion, because previous studies on isolated molecules indicated an energetic preference for the trans conformer. This study demonstrates that when packed into supramolecular lattices or crystals, peptoid polymers prefer to adopt a regular, extended, all-cis secondary structure.