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Die Erweiterung der chemischen Vielfalt von Peptid‐Makrozyklenbibliotheken für die Display‐Selektion ist wünschenswert, um ihr Potenzial zur Bindung an biomolekulare Ziele zu verbessern. Wir haben nun eine erhebliche Erweiterung durch die Einbeziehung eines großen, aromatischen helikalen Foldamers umgesetzt. Es wurde ein helikales aromatisches Foldamer identifiziert, welches eine Flexizym‐vermittelte tRNA‐Acylierung durchläuft und in der Lage ist, die ribosomale Translation mit Ausbeuten durchzuführen, die ausreichend hoch sind, um eine mRNA‐Display‐Selektion von makrozyklischen‐Foldamer‐Peptid‐Hybriden zu vollziehen. Ein hybrider Makrozyklus mit nanomolarer Affinität an C‐lobe der E6AP HECT‐Domäne wurde ausgewählt, der eine stark konvergente Peptidsequenz aufwies. Eine Kristallstruktur und Moleküldynamik‐Simulationen haben gezeigt, dass sowohl das Peptid als auch das Foldamer in einer faszinierenden, reziproken Heftklammer‐artigen Art helikal sind. Die starke Konvergenz der Reste könnte durch ihre Beteiligung an spezifischen Wechselwirkungen mit dem Zielprotein erklärt werden. Das Foldamer stabilisiert die Peptidhelix durch Heftklammern und durch Kontakte mit wesentlichen Resten. Diese Ergebnisse stellen insgesamt eine erhebliche Erweiterung des chemischen Raums dar, der für die Display‐Selektion zur Verfügung steht, und unterstreichen die möglichen Vorteile des Einfügens eines aromatischen Foldamers in einen Peptidmakrozyklus zum Zwecke der Proteinerkennung. [ABSTRACT FROM AUTHOR]

Durch die Entwicklung immer komplexerer Foldamere wird die Orchestrierung noch größerer Konformationsänderungen ermöglicht. Aromatische Faltblätter – ein seltenes Motiv in synthetischen Foldamer‐Strukturen – wurden so entwickelt, dass sie eigenständige Stapel bilden, was durch Selbstassemblierung zweier identischer Untereinheiten und Interkalation aromatischer Stränge ermöglicht wird. Ionen‐Mobilitäts‐ESI‐MS bestätigt die Bildung kompakter Dimere. Röntgenkristallographie zeigt die Existenz zweier Dimerzuständen mit unterschiedlichen Konformationen auf, die nur bei großer Veränderung ineinander interkonvertieren. Die Moleküldynamik‐Simulation validiert die Stabilität beider Konformationen sowie die Möglichkeit ihrer Interkonvertierung. [ABSTRACT FROM AUTHOR]

Die Chemie jenseits des Moleküls basiert auf schwachen, nicht‐kovalenten und damit reversiblen Wechselwirkungen. Als Folge dieser schwachen Bindungen kann eine strukturelle Organisation durch Faltung und Selbstorganisation üblicherweise nur für größere Moleküle stattfinden, die multiple Kontaktstellen aufweisen. Heute lassen sich solche "Supramoleküle" synthetisieren und ihre Faltungen in gewünschte Konformationen vorhersagen. Durch das Schaffen nicht‐natürlicher Einheiten, die aus molekularen Bausteinen mit definierten Sekundärstrukturen bestehen, kann eine neue Ebene der Chemie realisiert werden. Hier definieren wir diese Bausteine als "supramolekulare Elemente". Wir erwarten, dass eine zunehmende Ausrichtung der Forschung auf große Moleküle Konstruktionsprinzipien aufdecken wird, die von wiederkehrenden Motiven beherrscht werden, welche die Strukturbildung durch Faltung und Selbstorganisation steuern. Diese Prinzipien sind mit der Organisation von Atomen im Periodensystem der Elemente vergleichbar. Daher können diese Organisationsprinzipien auch zur Entwicklung eines Periodensystems der supramolekularen Elemente führen. [ABSTRACT FROM AUTHOR]

The recognition of either homomeric or heteromeric pairs of pentoses in an aromatic oligoamide double helical foldamer capsule was evidenced by circular dichroism (CD), NMR spectroscopy, and X‐ray crystallography. The cavity of the host was predicted to be large enough to accommodate simultaneously two xylose molecules and to form a 1:2 complex (one container, two saccharides). Solution and solid‐state data revealed the selective recognition of the α‐4C1‐d‐xylopyranose tautomer, which is bound at two identical sites in the foldamer cavity. A step further was achieved by sequestering a heteromeric pair of pentoses, that is, one molecule of α‐4C1‐d‐xylopyranose and one molecule of β‐1C4‐d‐arabinopyranose despite the symmetrical nature of the host and despite the similarity of the guests. Subtle induced‐fit and allosteric effects are responsible for the outstanding selectivities observed. [ABSTRACT FROM AUTHOR]

Derivatives of 4‐aminomethyl‐l‐phenylalanine with aromatic oligoamide foldamers as sidechain appendages were successfully charged on tRNA by means of flexizymes. Their subsequent incorporation both at the C‐terminus of, and within, peptide sequences by the ribosome, was demonstrated. These results expand the registry of chemical structures tolerated by the ribosome to sidechains significantly larger and more structurally defined than previously demonstrated. [ABSTRACT FROM AUTHOR]

Eine Wasserstoffbrücken‐Interaktionsfläche zwischen helikalen aromatischen Oligoamidfoldameren wurde gezielt entworfen, um die Bildung eines Helix‐Turn‐Helix‐Motivs mit einer Kopf‐zu‐Schwanz‐Anordnung zweier Helices unterschiedlicher Händigkeit zu ermöglichen. Dieses Design ist komplementär zu einem früheren Helix‐Turn‐Helix‐Motiv mit einer Kopf‐zu‐Kopf‐Anordnung zweier Helices identischer Händigkeit. Beide Motive zeigen eine vergleichbare Stabilität und führen, wenn sie miteinander kombiniert werden, zu einer unimolekularen Tetra‐Helix‐Anordnung, welche die bisher größte abiotische tertiäre Struktur darstellt. [ABSTRACT FROM AUTHOR]

An aromatic oligoamide sequence composed of a light‐responsive diazaanthracene‐based aromatic β‐sheet flanked by two variable diameter helical segments was prepared. Structural investigations revealed that such oligomers adopt two distinct conformations: a canonical symmetrical conformation with the two helices stacked above and below the sheet, and an unanticipated unsymmetrical conformation in which one helix has flipped to directly stack with the first helix. Photoirradiation of the foldamer led to the quantitative, and thermally reversible, formation of a single photoproduct resulting from the [4+4] cycloaddition of two diazaanthracenes within the aromatic β‐sheet. NMR and crystallographic studies revealed a parallel arrangement of the diazaanthracene photoproduct and a complete conversion into a symmetrical conformation requiring a rearrangement of all unsymmetrical conformers. These results highlight the potential of foldamers, with structures more complex than isolated helices, for the design of photoswitches showing nontrivial nanometer scale shape changes. [ABSTRACT FROM AUTHOR]

Peptide‐mediated self‐assembly is a prevalent method for creating highly ordered supramolecular architectures. Herein, we report the first example of orthogonal C−X⋅⋅⋅X−C/C−X⋅⋅⋅π halogen bonding and hydrogen bonding driven crystalline architectures based on synthetic helical peptides bearing hybrids of l‐sulfono‐γ‐AApeptides and natural amino acids. The combination of halogen bonding, intra‐/intermolecular hydrogen bonding, and intermolecular hydrophobic interactions enabled novel 3D supramolecular assembly. The orthogonal halogen bonding in the supramolecular architecture exerts a novel mechanism for the self‐assembly of synthetic peptide foldamers and gives new insights into molecular recognition, supramolecular design, and rational design of biomimetic structures. [ABSTRACT FROM AUTHOR]

We have investigated the self‐assembly of a dissymmetrical aromatic oligoamide helix on linear amido‐carbamate rods. A dissymmetric sequence bearing two differentiated ends is able to wrap around dissymmetric dumbbell guest molecules. Structural and thermodynamic investigations allowed us to decipher the mode of binding of the helix that can bind specifically to the amide and carbamate groups of the rod. In parallel kinetic studies of threading and sliding of the helix along linear axles were also monitored by 1H NMR. Results show that threading of a dissymmetrical host can be kinetically biased by the nature of the guest terminus allowing a preferential sense of sliding of the helix. The study presented below further demonstrates the valuable potential of foldaxanes to combine designed molecular recognition patterns with fine control of self‐assembly kinetics to conceive complex supramolecular events. [ABSTRACT FROM AUTHOR]

The potential of structured peptides has not been explored much in the design of metal‐organic frameworks (MOFs). This is partly due to the difficulties in obtaining stable secondary structures from the short α‐peptide sequences. Here we report the design, crystal conformations, coordination site dependent different silver coordinated frameworks of short α,γ‐hybrid peptide 12‐helices consisting of terminal pyridyl moieties and the utility of metal‐helix frameworks in the adsorption of CO2. Upon silver ion coordination the 12‐helix terminated by the 3‐pyridyl derivatives adopted a 2:2 macrocyclic structure, while the 12‐helix terminated by the 4‐pyridyl derivatives displayed remarkable porous metal‐helix frameworks. Both head‐to‐tail intermolecular H‐bonds of the 12‐helix and metal ion coordination have played an important role in stabilizing the ordered metal‐helix frameworks. The studies described here open the door to design a new class of metal‐organic‐frameworks from peptide foldamers. [ABSTRACT FROM AUTHOR]

Halogen bonding has been used to glue together hydrogen‐bonded short arylamide foldamers to achieve new supramolecular double and quadruple helices in the solid state. Three compounds, which bear a pyridine at one end and either a CF2I or fluorinated iodobenzene group at the other end, engage in head‐to‐tail N⋅⋅⋅I halogen bonds to form one‐component supramolecular P and M helices, which stack to afford supramolecular double‐stranded helices. One of the double helices can dimerize to form a G‐quadruplex‐like supramolecular quadruple helix. Another symmetric compound, which bears a pyridine at each end, binds to ICF2CF2I through N⋅⋅⋅I halogen bonds to form two‐component supramolecular P and M helices, with one turn consisting of four (2+2) molecules. Half of the pyridine‐bearing molecules in two P helices and two M helices stack alternatingly to form another supramolecular quadruple helix. Another half of the pyridine‐bearing molecules in such quadruple helices stack alternatingly with counterparts from neighboring quadruple helices, leading to unique quadruple helical arrays in two‐dimensional space. [ABSTRACT FROM AUTHOR]

Abstract: Xylobiose sequestration in a helical aromatic oligoamide capsule was evidenced by circular dichroism, NMR spectroscopy, and crystallography. The preparation of the 5 kDa oligoamide sequence was made possible by the transient use of acid‐labile dimethoxybenzyl tertiary amide substituents that disrupt helical folding and prevent double helix formation. Binding of other disaccharides was not detected. Crystallographic data revealed a complex composed of a d‐xylobiose α anomer and two water molecules accommodated in the right‐handed helix. The disaccharide was found to adopt an unusual all‐axial compact conformation. A dense network of 18 hydrogen bonds forms between the guest, the cavity wall, and the two water molecules. [ABSTRACT FROM AUTHOR]

Abstract: A simple, unsaturated, E–Z photoisomerizable β‐amino acid, (Z)‐3‐aminoprop‐2‐enoic acid, has been introduced into peptide foldamers through a one‐pot chemical coupling, based on Pd/Cu‐catalyzed olefin oxidative amidation, between two peptide segments carrying, respectively, a ‐Gly‐NH2 residue at the C‐terminus and an acryloyl group at the N‐terminus. Reversible conversion between the Z and E configurations of the 3‐aminoprop‐2‐enoic linkage was achieved photochemically. A crystallographic analysis on two model compounds shed light on the consequences, in terms of 3D structure and self‐association properties, brought about by the different configuration of the unsaturated linkage. As a proof of concept, E–Z photoisomerization of a 3‐aminoprop‐2‐enoic acid residue, inserted as the junction between two conformationally distinct peptide domains (one helical while the other β‐sheet promoter), allowed supramolecular self‐association to be reversibly turned on/off. [ABSTRACT FROM AUTHOR]

Abstract: Foldamers are an important class of abiotic macromolecules, with potential therapeutic applications in the disruption of protein–protein interactions. The majority adopt a single conformational motif such as a helix. A class of foldamer is now introduced where the choice of heterocycle within each monomer, coupled with a strong conformation‐determining dipole repulsion effect, allows both helical and extended conformations to be selected. Combining these monomers into hetero‐oligomers enables highly controlled exploration of conformational space and projection of side‐chains along multiple vectors. The foldamers were rapidly constructed via an iterative deprotection‐cross‐coupling sequence, and their solid‐ and solution‐phase conformations were analysed by X‐ray crystallography and NMR and CD spectroscopy. These molecules may find applications in protein surface recognition where the interface does not involve canonical peptide secondary structures. [ABSTRACT FROM AUTHOR]

Abstract: Metal–ligand coordination is a key interaction in the self‐assembly of both biopolymers and synthetic oligomers. Although the binding of metal ions to synthetic proteins and peptides is known to yield high‐order structures, the self‐assembly of peptidomimetic molecules upon metal binding is still challenging. Herein we explore the self‐assembly of three peptoid trimers bearing a bipyridine ligand at their C‐terminus, a benzyl group at their N‐terminus, and a polar group (N‐ethyl‐R) in the middle position (R=OH, OCH3, or NH2) upon Cu2+ coordination. X‐ray diffraction analysis revealed unique, highly symmetric, dinuclear cyclic structure or aqua‐bridged dinuclear double‐stranded peptoid helicates, formed by the self‐assembly of two peptoid molecules with two Cu2+ ions. Only the macrocycle with the highest number of intermolecular hydrogen bonds is stable in solution, while the other two disassemble to their corresponding monometallic complexes. [ABSTRACT FROM AUTHOR]

Abstract: Double helices are not common in polypeptides and proteins except in the peptide antibiotic gramicidin A and analogous l,d‐peptides. In contrast to natural polypeptides, remarkable β‐double‐helical structures from achiral γ‐peptides built from α,β‐unsaturated γ‐amino acids have been observed. The crystal structures suggest that they adopted parallel β‐double helical structures and these structures are stabilized by the interstrand backbone amide H‐bonds. Furthermore, both NMR spectroscopy and fluorescence studies support the existence of double‐helical conformations in solution. Although a variety of folded architectures featuring distinct H‐bonds have been discovered from the β‐ and γ‐peptide foldamers, this is the first report to show that achiral γ‐peptides can spontaneously intertwine into β‐double helical structures. [ABSTRACT FROM AUTHOR]

The development of foldamer-based receptors is driven by the design of monomers with specific properties. Herein, we introduce a pyridazine-pyridine-pyridazine diacid monomer and its incorporation into helical aromatic oligoamide foldamer containers. This monomer codes for a wide helix diameter and can sequester metal ions on the inner wall of the helix cavity. Crystallographic studies and NMR titrations show that part of the metal coordination sphere remains available and may then promote the binding of a guest within the cavity. In addition to metal coordination, binding of the guest is assisted by cooperative interactions with the helix host, thereby resulting in significant enhancements depending on the foldamer sequence, and in slow guest capture and release on the NMR time scale. In the absence of metal ions, the pyridazine-pyridine-pyridazine monomer promotes an extended conformation of the foldamer that results in aggregation, including the formation of an intertwined duplex. [ABSTRACT FROM AUTHOR]

A linear molecular architecture equipped with complementary three-fold hydrogen-bonding units embedded with a photoswitchable trans-tetrafluoroazobenzene moiety was synthesized. The transto cis photoisomerism of the azobenzene unit induced drastic changes in the molecular architecture as a result of intramolecular hydrogen bonding as evidenced by NMR spectroscopy and size exclusion chromatography. A minute stereogenic element in the linear trans state enabled stereoselective folding into the cis state, thus producing a globular architecture with enhanced chiroptical property. [ABSTRACT FROM AUTHOR]

The conformational heterogeneity of backbone N-substituted peptides limits their ability to adopt stable secondary structures. Herein, we describe a practical synthesis of backbone aminated peptides that readily adopt β-sheet folds. Data derived from model N-amino peptides suggest that extended conformations are stabilized through cooperative steric, electrostatic, and hydrogen-bonding interactions. [ABSTRACT FROM AUTHOR]

Peptide foldamers containing both cis-β-aminocyclopentanecarboxylic acid and α-amino acid residues combined in various sequence patterns (ααβ, αααβ, αβααβ, and ααβαααβ) were screened using CD and NMR spectroscopy for the tendency to form helices. ααβ-Peptides were found to fold into an unprecedented and well-defined 16/17/15/18/14/17-helix. By extending the length of the sequence or shifting a fragment of the sequence from one terminus to another in ααβ-peptides, the balance between left-handed and right-handed helix populations present in the solution can be controlled. Engineering of the peptide sequence could lead to compounds with either a strong propensity for the selected helix sense or a mixture of helical conformations of opposite senses. [ABSTRACT FROM AUTHOR]

The re-emergence of influenza raises a global concern that viral pandemics can unpredictably occur. However, effective approaches that can probe the infection risk of influenza viruses for humans are rare. In this work, we develop a glycofoldamer that can rapidly identify the glycan-receptor specificity of influenza viruses in a high-throughput manner. The coupling of glycan receptors that can be recognized by hemagglutinin (a surface protein on the virion capsid of influenza) to a fluorogenic-dye foldamer produces the glycofoldamers with minimal fluorescence in aqueous solution. After interaction with human-infecting virus strains for only five minutes, the fluorescence intensity of the glycofoldamer is remarkably enhanced with a blue-shifted emission peak. The probes have also proven effective for the rapid identification of 1) the human- or bird-infecting properties of influenza viruses in a high-throughput manner and 2) the receptor-specificity switch of a virus strain by mutations. [ABSTRACT FROM AUTHOR]

A major current challenge in bioorganic chemistry is the identification of effective mimics of protein secondary structures that act as inhibitors of protein-protein interactions (PPIs). In this work, trans-2-aminocyclobutanecarboxylic acid ( tACBC) was used as the key β-amino acid component in the design of α/β/γ -peptides to structurally mimic a native α-helix. Suitably functionalized α/β/γ-peptides assume an α-helix-mimicking 12,13-helix conformation in solution, exhibit enhanced proteolytic stability in comparison to the wild-type α-peptide parent sequence from which they are derived, and act as selective inhibitors of the p53/ hDM2 interaction. [ABSTRACT FROM AUTHOR]

Oligoureas (up to n=6) of meso cyclohexane-1,2-diamine were synthesized by chain extension with an enzymatically desymmetrized monomer 2. Despite being achiral, the meso oligomers adopt chiral canonical 2.5-helical conformations, the equally populated enantiomeric screw-sense conformers of which are in slow exchange on the NMR timescale, with a barrier to screw-sense inversion of about 70 kJ mol−1. Screw-sense inversion in these helical foldamers is coupled with cyclohexane ring-flipping, and results in a reversal of the directionality of the hydrogen bonding in the helix. The termini of the meso oligomers are enantiotopic, and desymmetrized analogues of the oligoureas with differentially and enantioselectively protected termini display moderate screw-sense preferences. A screw-sense preference may furthermore be induced in the achiral, meso oligoureas by formation of a 1:1 hydrogen-bonded complex with the carboxylate anion of Boc- d-proline. The meso oligoureas are the first examples of hydrogen-bonded foldamers with reversible hydrogen-bond directionality. [ABSTRACT FROM AUTHOR]

The impact of geometrically constrained cis α,β-unsaturated γ-amino acids on the folding of α,γ-hybrid peptides was investigated. Structure analysis in single crystals and in solution revealed that the cis carbon-carbon double bonds can be accommodated into the 12-helix without deviation from the overall helical conformation. The helical structures are stabilized by 4→1 hydrogen bonding in a similar manner to the 12-helices of β-peptides and the 310 helices of α-peptides. These results show that functional cis carbon-carbon double bonds can be accommodated into the backbone of helical peptides. [ABSTRACT FROM AUTHOR]

Disulfide bridge formation was investigated in helical aromatic oligoamide foldamers. Depending on the position of thiol-bearing side chains, exclusive intramolecular or intermolecular disulfide bridging may occur. The two processes are capable of self-sorting, presumably by dynamic exchange. Quantitative assessment of helix handedness inversion rates showed that bridging stabilizes the folded structures. Intermolecular disulfide bridging serendipitously yielded a well-defined, C2-symmetrical, two-helix bundle-like macrocyclic structure in which complete control over relative handedness, that is, helix-helix handedness communication, is mediated remotely by the disulfide bridged side chains in the absence of contacts between helices. MM calculations suggest that this phenomenon is specific to a given side chain length and requires disulfide functions [ABSTRACT FROM AUTHOR]

Small changes in the structure of a foldamer may lead to gross changes in conformational preference. We show that the simple insertion or deletion of a single hydrogen bond by changes in pH or by photochemical deprotection is sufficient to refold a helical oligomer, interconverting M and P screw-sense preference. As a consequence of the switch, information may be transmitted to a remote catalytic site, selectively directing the formation of either of two enantiomeric products by a reaction involving 1,22-remote intermolecular asymmetric induction. [ABSTRACT FROM AUTHOR]

Abiotic aromatic oligoamide foldamers are shown to self-assemble in solution to form a double helix, which can accommodate a bichromophoric thread in its central void. While in solution reversible electronic energy transfer is instilled between chromophoric termini of the free, flexible thread as evidenced through delayed luminescence, upon rigidification of the rod the chromophores are mutually distanced and effectively decoupled. Consequently, the chromophores display their individual photophysical characteristics. The observed conformation-dependent changes of dynamic luminescence properties, which are particularly sensitive to distance, offers a new strategy for lifetime-based detection of geometry on the molecular scale as demonstrated through real-time luminescence detection of molecular complexation leading to foldaxane formation. [ABSTRACT FROM AUTHOR]

The conformational control of molecular scaffolds allows the display of functional groups in defined spatial arrangement. This is of considerable interest for developing fundamental and applied systems in both the fields of biology and material sciences. Peptides afford a large diversity of functional groups, and peptide synthetic routes are very attractive and accessible. However, most short peptides do not possess well-defined secondary structures. Herein, we developed a simple strategy for converting peptide sequences into structured g-lactam-containing oligomers while keeping the amino acids side chain diversity. We showed the propensity of these molecules to adopt ribbon-like secondary structures. The periodic distribution of the functional groups on both sides of the ribbon plane is encoded by the initial peptide sequence. [ABSTRACT FROM AUTHOR]

The creation of self-assembling microscale architectures that possess new and useful physical properties remains a significant challenge. Herein we report that an 11-helical foldamer self-assembles in a controlled manner to form a series of 3D foldectures with unusual three-fold symmetrical shapes that are distinct from those generated from 12-helical foldamers. The foldamer packing motif was revealed by powder X-ray diffraction technique, and provides an important link between the molecular-level symmetry and the microscale morphologies. The utility of foldectures with hollow interiors as robust and well-defined supramolecular hosts was demonstrated for inorganic, organic, and even protein guests. This work will pave the way for the design of functional foldectures with greater 3D shape diversity and for the development of biocompatible delivery vehicles and containment vessels. [ABSTRACT FROM AUTHOR]

Despite significant advances in foldamer chemistry, tailored delivery systems based on foldamer architectures, which provide a high level of control over secondary structure, are curiously rare among non-viral technologies for transporting nucleic acids into cells. A potent pH-responsive, bioreducible cell-penetrating foldamer (CPF) was developed through covalent dimerization of a short (8-mer) amphipathic oligourea sequence bearing histidine-type units. This CPF exhibits a high capacity to assemble with pDNA and mediates efficient delivery of nucleic acids into the cell. Furthermore, it does not adversely affect cellular viability and was shown to compare favorably with a cognate peptide transfection agent based on His-rich sequences. [ABSTRACT FROM AUTHOR]

Cyclic homologated amino acids are important building blocks for the construction of helical foldamers. N-aminoazetidine-2-carboxylic acid (AAzC), an aza analogue of trans-2-aminocyclobutanecarboxylic acid ( tACBC), displays a strong hydrazino turn conformational feature, which is proposed to act as an 8-helix primer. tACBC oligomers bearing a single N-terminal AAzC residue were studied to evaluate the ability of AAzC to induce and support an 8-helix along the oligopeptide length. While tACBC homooligomers assume a dominant 12-helix conformation, the aza-primed oligomers preferentially adopt a stabilized 8-helix conformation for an oligomer length up to 6 residues. The (formal) single-atom exchange at the N terminus of a tACBC oligomer thus contributes to the sustainability of the 8-helix, which resists the switch to a 12-helix. This effect illustrates atomic-level programmable design for fine tuning of peptide foldamer architectures. [ABSTRACT FROM AUTHOR]

Short α-peptides with less than 10 residues generally display a low propensity to nucleate stable helical conformations. While various strategies to stabilize peptide helices have been previously reported, the ability of non-peptide helical foldamers to stabilize α-helices when fused to short α-peptide segments has not been investigated. Towards this end, structural investigations into a series of chimeric oligomers obtained by joining aliphatic oligoureas to the C- or N-termini of α-peptides are described. All chimeras were found to be fully helical, with as few as 2 (or 3) urea units sufficient to propagate an α-helical conformation in the fused peptide segment. The remarkable compatibility of α-peptides with oligoureas described here, along with the simplicity of the approach, highlights the potential of interfacing natural and non-peptide backbones as a means to further control the behavior of α-peptides. [ABSTRACT FROM AUTHOR]

Two dynamic covalent polymers P1 and P2 were prepared by alternately linking electron-rich tetrathiafulvalene (TTF) and electron-deficient bipyridinium (BIPY2+) through hydrazone bonds. In acetonitrile, the polymers were induced by intramolecular donor-acceptor interactions to form pleated foldamers, which unfolded upon oxidation of the TTF units to the radical cation TTF.+. Reduction of the BIPY2+ units to BIPY.+ led to the formation of another kind of pleated secondary structures, which are stabilized by intramolecular dimerization of the BIPY.+ units. The diradical dicationic cyclophane cyclobis(paraquat- p-phenylene) (CBPQT2(.+)) could further force the folded structures to unfold by including the BIPY.+ units of the polymers. Upon oxidation of the BIPY.+ units of the cyclophane and polymers to BIPY2+, the first folded state was regenerated. Switching or conversion between the four conformational states was confirmed by UV/Vis spectroscopic experiments. [ABSTRACT FROM AUTHOR]

Inhibition of protein-protein interactions (PPIs) represents a major challenge in chemical biology and drug discovery. α-Helix mediated PPIs may be amenable to modulation using generic chemotypes, termed 'proteomimetics', which can be assembled in a modular manner to reproduce the vectoral presentation of key side chains found on a helical motif from one partner within the PPI. In this work, it is demonstrated that by using a library of N-alkylated aromatic oligoamide helix mimetics, potent helix mimetics which reproduce their biophysical binding selectivity in a cellular context can be identified. [ABSTRACT FROM AUTHOR]

α,β-Hybrid oligomers of varying lengths with alternating proteogenic α-amino acid and the rigid β2,3,3-trisubstituted bicyclic amino acid ABOC residues were studied using both X-ray crystal and NMR solution structures. While only an 11/9 helix was obtained in the solid state regardless of the length of the oligomers, conformational polymorphism as a chain-length-dependent phenomenon was observed in solution. Consistent with DFT calculations, we established that short oligomers adopted an 11/9 helix, whereas an 18/16 helix was favored for longer oligomers in solution. A rapid interconversion between the 11/9 helix and the 18/16 helix occurred for oligomers of intermediate length. [ABSTRACT FROM AUTHOR]

The postsynthetic modulation of capsules based on helical aromatic oligoamide foldamers would be a powerful approach for controlling their receptor properties without altering the initial monomer sequences. With the goal of developing a method to increase the size of a cavity within a helix, a single-helical foldamer capsule was synthesized with a wide-diameter central segment that was designed to intercalate with a second shorter helical strand. Despite the formation of stable double-helical homodimers ( Kdim>107 M−1) by the shorter strand, when it was mixed with the single-helical capsule sequence, a cross-hybridized double helix was formed with Ka>105 M−1. This strategy makes it possible to direct the formation of double-helical heterodimers. On the basis of solution- and solid-state structural data, this intercalation resulted in an increase in the central-cavity size to give a new interior volume of approximately 150 Å3. [ABSTRACT FROM AUTHOR]

Foldamers are non-natural oligomers that adopt stable conformations reminiscent of those found in proteins. To evaluate the potential of foldameric subunits for catalysis, semisynthetic enzymes containing foldamer fragments constructed from α- and β-amino acid residues were designed and characterized. Systematic variation of the α→β substitution pattern and types of β-residue afforded highly proficient hybrid catalysts, thus demonstrating the feasibility of expanding the enzyme-engineering toolkit with non-natural backbones. [ABSTRACT FROM AUTHOR]

In the search of molecules that could recognize sizeable areas of protein surfaces, a series of ten helical aromatic oligoamide foldamers was synthesized on solid phase. The foldamers comprise three to five monomers carrying various proteinogenic side chains, and exist as racemic mixtures of interconverting right-handed and left-handed helices. Functionalization of the foldamers by a nanomolar ligand of human carbonic anhydrase II (HCA) ensured that they would be held in close proximity to the protein surface. Foldamer-protein interactions were screened by circular dichroism (CD). One foldamer displayed intense CD bands indicating that a preferred helix handedness is induced upon interacting with the protein surface. The crystal structure of the complex between this foldamer and HCA could be resolved at 2.1 Å resolution and revealed a number of unanticipated protein-foldamer, foldamer-foldamer, and protein-protein interactions. [ABSTRACT FROM AUTHOR]

Konformationsänderungen des konjugierten Rückgrats von Poly ‐ und Oligodiacetylenen (PDAs und ODAs) spielen bei der Bestimmung der elektronischen Eigenschaften dieser Verbindungen eine wichtige Rolle. Gleichzeitig können Konformationsänderungen auch zu gefalteten Strukturen führen, die helikale Chiralität aufweisen. Durch Verwendung von D ‐ Campher als chiraler Baustein konnten monodisperse, optisch reine cis ‐ Oligodiacetylene (ODAs) in hoher Ausbeute erhalten werden. cis ‐ ODAs bis zur Länge des Tridecamers wurden synthetisiert, was dem längsten bisher bekannten monodispersen cis ‐ ODA entspricht. UV/Vis ‐ Spektroskopie deutet auf eine hohe effektive Konjugationslänge in THF hin, vermutlich aufgrund einer linearen planaren Konformation in diesem Lösungsmittel. Hochauflösende STM/AFM ‐ Messungen von Filmen des Nonamers, abgeschieden aus einer THF ‐ Lösung auf HOPG, zeigen eine lineare Struktur. In iPrOH gemessene Zirkulardichroismus(CD) ‐ Spektren legen die Bildung chiraler Aggregate der ODAs mit mindestens neun D ‐ Campher ‐ Einheiten nahe. Die CD ‐ Resonanz ist konzentrations ‐ und temperaturabhängig. Lösungsmitteleffekte: Die Synthese und Charakterisierung von optisch reinen, monodispersen cis ‐ ODAs basierend auf D ‐ Campher ‐ Bausteinen wird beschrieben. Die Reihe der Oligomere wurde bis zur Länge des Tridecamers synthetisiert, welches zugleich das längste bisher bekannte cis ‐ ODA darstellt. Mit optischer Spektroskopie und STM/AFM ‐ Messungen wurde nachgewiesen, dass die Oligomere in THF gelöst eine lineare planare Konformation annehmen. Umgekehrt bilden die ODAs in iPrOH chirale Aggregate, sobald n≥9. [ABSTRACT FROM AUTHOR]

Zwei photoschaltbare Foldamere, die Azobenzol ‐ Einheiten als Energie ‐ Akzeptoren beinhalten, wurden entwickelt. Ihr Entfaltungsmechanismus kann durch den kontrollierten Einbau dieser photoinduzierten Auslöser (rot) in der Mitte (links) oder an den Enden (rechts) der Helix gesteuert werden. [ABSTRACT FROM AUTHOR]

Der Regenbogen der Pyrrolidine: Rot Orange Gelb Grün Blau (Indigo Violett) [ABSTRACT FROM AUTHOR]

Mit Röntgen ‐ Kristallographie wurden Strukturen der α/β ‐ Peptid ‐ 11/9 ‐ Helix bestimmt. Die racemischen Verbindungen zeigen eine zentrosymmetrische Kristallpackung mit vollständig gefalteten 11/9 ‐ Helixkonformationen. Abgesehen von den unterschiedlichen Wasserstoffbrücken sind die Parameter der 11/9 ‐ Helix analog zu denen der 310 ‐ Helix. [ABSTRACT FROM AUTHOR]

Außen racemisch, innen nicht: Wirte aus aromatischen Foldameren sind Enantiomere und ziehen es als solche vor, zu cokristallisieren, auch wenn ihre Gäste (z. B. L ‐ Weinsäure, siehe Bild) nicht als Enantiomere vorliegen. Dieses Verhalten ermöglicht die Strukturaufklärung von diastereomeren und quasiracemischen Strukturen im Festkörper in einem Schritt. [ABSTRACT FROM AUTHOR]

Ein biomimetischer Ansatz liegt der Selbstorganisation eines helikalen Poly(para ‐ aryltriazol) ‐ Foldamers um ein Templat zugrunde. Diese solvophobe Faltung ergibt Helices, die sich weiterhin zu langen Nanoröhren zusammenlagern (siehe Bild; Maßstab: 100 nm). Konstrukte einer bestimmten Länge und Chiralität werden mit dem Poly(γ ‐ benzyl ‐ L ‐ glutamat) ‐ Gerüst unter geeigneten Bedingungen erhalten, wie beim selbstorganisierten Aufbau von Tabakmosaikviren. [ABSTRACT FROM AUTHOR]

9 ‐ Helix: 4 ‐ Amino(methyl) ‐ 1,3 ‐ thiazol ‐ 5 ‐ carbonsäuren (ATCs) wurden als neue γ ‐ Aminosäure ‐ Bausteine hergestellt. Die Strukturen verschiedener ATC ‐ Oligomere wurden in Lösung mit CD ‐ und NMR ‐ Spektroskopie und im festen Zustand durch Kristallstrukturanalyse untersucht. Die ATC ‐ Sequenzen nehmen eine wohldefinierte 9 ‐ Helix ‐ Struktur ein, sowohl im festen Zustand als auch in aprotischen und protischen organischen Lösungsmitteln und in wässriger Lösung. [ABSTRACT FROM AUTHOR]

Eine Reihe von Peptoiden, oder Oligomeren N ‐ substituierter Glycine, nimmt die neuartige Sekundärstruktur des „Peptoid ‐ Bands“ ein. Diese Faltungsweise ist bei geringen Kettenlängen und in vielfältigen Medien (organisch und wässrig) stabil und folgt aus einer Primärsequenz von Peptoidmonomeren, die eine abwechselnde cis ‐ und trans ‐ Anordnung der Amidgruppen in der Hauptkette erzwingt. [ABSTRACT FROM AUTHOR]

Gib ihnen Struktur: Die Gegenwart strukturierender Elemente in mit katalytischen Einheiten funktionalisierten Polymeren ergab eine neue Klasse von Enzymmimetika, die nur im gefalteten Zustand aktiv sind (siehe Bild). Die konformativ anpassungsfähige hydrophobe Umgebung um das katalytische Zentrum ermöglicht die hocheffiziente Katalyse einer Aldolreaktion in Wasser mit Michaelis ‐ Menten ‐ Kinetik. [ABSTRACT FROM AUTHOR]