Noncovalent Association Research Articles

Beyond Sequencing: Prioritizing and Delivering Neoantigens for Cancer Vaccines.

Neoantigens are tumor-specific proteins and peptides that can be highly immunogenic. Immune-mediated tumor rejection is strongly associated with cytotoxic responses to neoantigen-derived peptides in noncovalent association with self-HLA molecules. Neoantigen-based therapies, such as adoptive T cell transfer, have shown the potential to induce remission of treatment-resistant metastatic disease in select patients. Cancer vaccines are similarly designed to elicit or amplify antigen-specific T cell populations and stimulate directed antitumor immunity, but the selection and prioritization of the neoantigens remains a challenge. Bioinformatic algorithms can predict tumor neoantigens from somatic mutations, insertion-deletions, and other aberrant peptide products, but this often leads to hundreds of potential neoepitopes, all unique for that tumor. Selecting neoantigens for cancer vaccines is complicated by the technical challenges of neoepitope discovery, the diversity of HLA molecules, and intratumoral heterogeneity of passenger mutations leading to immune escape. Despite strong preclinical evidence, few neoantigen cancer vaccines tested in vivo have generated epitope-specific T cell populations, suggesting suboptimal immune system activation. In this chapter, we review factors affecting the prioritization and delivery of candidate neoantigens in the design of therapeutic and preventive cancer vaccines and consider synergism with standard chemotherapies.

The covalent complex of Jo-In results from a long-lived, non-covalent intermediate state with near-native structure

Covalent protein complexes have been used to assemble enzymes in large scaffolds for biotechnology purposes. Although the catalytic mechanism of the covalent linking of such proteins is well known, the recognition and overall structural mechanisms driving the association are far less understood but could help further functional engineering of these complexes. Here, we study the Jo-In complex by NMR spectroscopy and molecular modelling. We characterize a transient non-covalent complex, with structural elements close to those in the final covalent complex. Using site specific mutagenesis, we further show that this non-covalent association is essential for the covalent complex to form.

Methods for Small-Angle Scattering Measurements on Peptiplexes of DNA with Cell-Penetrating Peptides.

Peptiplexes are soft biomaterials formed through the noncovalent association between cell-penetrating peptides and nucleic acids. Although internalization often involves electrostatic anchoring followed by endocytosis, the mode of action of these transporters remains elusive in many cases, and proper understanding of mechanisms behind their penetrating capabilities necessarily entails structural data at the nanoscopic scale. In this chapter, we examine the structural landscape of peptiplexes, emphasizing the complex behavior of these polyelectrolyte self-assemblies and how supramolecular order impacts their translocation efficiency. We discuss experimental tools commonly used to investigate the structure of peptiplexes and pay special attention to small-angle X-ray scattering (SAXS) as a suitable method for unveiling their nanoscale organization. A roadmap for standard SAXS measurements in CPP/DNA samples is presented alongside a selection of observations from our own experience dealing with SAXS applied to the investigation of CPPs.

A Novel B Cell Antigen Designated Lambda Myeloma Antigen (LMA) Has Been Identified Using Two Fully Human Monoclonal Antibodies (Mabs) That Bind to Similar Epitopes on Plasma Cells from Patients with Plasma Cell Dyscrasias

Introduction:The novel kappa (κ) myeloma antigen (KMA) has been described and a specific monoclonal antibody KappaMab (formerly MDX-1097) developed which is currently in a Phase IIb clinical trial. In this study 2 human LambdaMabs (10B3 and 7F11) were shown to specifically bind to a conformational epitope in the lambda (λ) light chain constant region when it is held in non-covalent association with lipids in the cell membrane (LMA). The 10B3 Mab binds to all λ isotypes and 7F11 binds to isotypes 2 and 3; neither antibody binds κ light chain or immunoglobulin (Igλ or Igκ).Methods:To detect LMA on λ+ myeloma cell lines and on λ-restricted patient bone marrow (BM) samples, 7F11 and 10B3 Fab'2 fragments were conjugated to APC and R-PE and used to stain the λ myeloma cell lines LP-1, RPMI8226 and OPM-2 followed by flow cytometry analysis. KappaMab Fab'2 (KMA Fab'2) and the κ myeloma cell line JJN3 were used as a negative control and to identify KMA on κ-restricted patient BM samples.Patient BM samples (κ=43 and λ=22) included Monoclonal Gammopathy of Undetermined Significance (MGUS), untreated and treated multiple myeloma (MM) patients, AL amyloidosis, plasmacytoma and Waldenstroms macroglobulinemia (WM). Multiparametric FCM immunophenotyping was performed with the 10B3 Fab'2 fragments and CD38, CD138, CD269 (BCMA), CD319 (SLAM F7), CD56 and CD45 Mabs. Plasma cells (PCs) were identified by the co-expression of CD38 and CD138, then CD138+/CD38+ gated cells were analyzed for 10B3 or KMA, CD269, CD319, and CD56. KMA and LMA Fab'2 fragments were used as negative controls for each other. The antigen density of KMA or LMA versus BCMA on PCs in 55 samples was assessed using Quantibrite beads.Immunohistochemistry (ICH) tissue cross-reactivity studies using validated automated methods on tissue with whole antibody 7F11-biotin and 10B3-FITC were performed on MM cell lines, λ myeloma lung tissue (plasmacytoma) and a panel of 38 normal human tissues. Serial sections from snap frozen blocks were used to retain the conformational epitope and then stained with the λ Mabs and visualised by light microscopy.Results:The conjugated 10B3 Fab'2 fragment bound to LMA-expressing cell lines LP-1, RPMI8226 and OPM-2 (isotypes 1-3) and 7F11 bound to RPMI8226 and OPM-2, (isotypes 2-3); neither bound JJN3. KMA Fab'2 did not bind to λ myeloma cell lines but bound JJN3.Expression profiles for patient BM samples (Table 1) showed KMA was expressed on PCs from untreated (N=9/17; 53%) and treated (N=8/11; 73%) MM samples, whereas BCMA expression was 88% (N=15/17) and 82% (N=9/11) respectively. BM PCs from all 3 plasmacytoma cases and 1 WM case were positive for both KMA and BCMA. BM PCs from MGUS cases were all positive for BCMA and positive for KMA in half the cases studied. The expression of KMA and CD56 was highest on PCs from treated MM patient samples. Antigen density for KMA and BCMA was similar in the untreated patients. In treated patients KMA density was higher than BCMA, other samples had lower antigen density of both KMA and BCMA.LMA (Table 2) and BCMA were expressed on 50% and 90% of untreated MM samples and all LMA+ samples co-expressed BCMA but only 1 co-expressed CD56. All treated λMM samples expressed BCMA and 60% expressed LMA. LMA was positive on PCs from the 3 amyloidosis samples, BCMA was expressed weakly in only 1 of these whereas CD56 was always co-expressed with LMA. MGUS and WM samples did not express LMA. Similar to KMA, the antigen density of LMA and BCMA was equivalent in untreated patients but in treated patients LMA density was higher than BCMA. All 3 amyloidosis samples were λ isotype.IHC results showed that 10B3 and 7F11 bound to myeloma cell lines and 10B3 bound to PCs in λ plasmacytoma sections. Both Mabs bound occasional PCs or dendritic cells in the GI tract mucosa, tonsil and various secondary lymphoid organs. No off-target binding of 10B3 and 7F11 was observed and both antibodies bound occasional PCs in secondary lymphoid tissue.Conclusion:These studies used mostly myeloma samples and a small number of other plasma cell dyscrasias. Nevertheless expression of KMA and LMA was identified on PCs across the spectrum of disease. Within the treated patient cohort the antigen density of KMA or LMA was higher than that of BCMA and implies there is an enrichment of these novel antigens in relapsed refractory myeloma. No off-target binding was observed in normal human tissues and binding was limited to occasional leukocytes in secondary lymphoid tissue. [Display omitted] DisclosuresHu: HaemaLogiX Pty Ltd: Current Employment. Dunn: HaemaLogiX Pty Ltd: Current Employment.

Seven cocrystals of pyrazinamide and organic acids by H-bonds and some noncovalent associations

Pyrazinamide, (PZA), forms seven novel co-crystals with a series of organic acids: 2‑chloro-4-nitrophenol (cnp), o‑hydroxy-cinnamic acid (ohcina), p‑hydroxy-cinnamic acid (phcina), 4-hydroxymandelic acid (hmna), 2,6-dichlorobenzoic acid (dcba), 5-hydroxyisophthalic acid (hispta) and 2,5-thiophenedicarboxylic acid (tpda). These crystal structures were analyzed and characterized by mp, single crystal X-ray diffraction, and IR. Single crystal X-ray diffractions show that the classical hydrogen bonds play a key part in binding individual molecules into larger architectures, especially the strong NH···N, NH···O, OH···N and OH···O hydrogen bonds, weak but highly directional CH···O interactions exist commonly in all co-crystals. Deep view into the crystal packing unveil that a different array of additional CHN, CHO, CH-π, CHCH, CHCl, CC, OC, N-S, Cl-O, Cl-Cl and π-π contacts contribute to the stabilization and expansion of the total 3D nets. For the delicate balance of the various weak forces, these structures adopted homo or hetero supramolecular synthons or both. Particularly, apart from 1, all of the reported co-crystals share the widely common R22(8) synthon.

A Non-Covalent Dimer Formation of Quaternary Ammonium Cation with Unusual Charge Neutralization in Electrospray-Ionization Mass Spectrometry

Specific and nonspecific non-covalent molecular association of biomolecules is characteristic for electrospray-ionization mass spectrometry analysis of biomolecules. Understanding the interaction between two associated molecules is of significance not only from the biological point of view but also gas phase analysis by mass spectrometry. Here we reported a formation of non-covalent dimer of quaternary ammonium denatonium cation with +1 charge detected in the positive ion mode electrospray ionization mass spectrometry analysis of denatonium benzoate. Hydrogen deuterium exchange of amide and carbon-bonded hydrogens revealed that charge neutralization of one denatonium cation is the consequence of amide hydrogen dissociation. DFT (Density Functional Theory) calculations proved high thermodynamic stable of formed dimer stabilized by the short and strong N..H-N hydrogen bond. The signal intensity of the peak characterizing non-covalent dimer is low intensity and does not depend on the sample concentration. Additionally, dimer observation was found to be instrument-dependent. The current investigation is the first experimental and theoretical study on the quaternary ammonium ions dimer. Thus the present study has great significance for understanding the structures of the biomolecules as well as materials.

Novel quaternary structures of the human prion protein globular domain

Prion disease is caused by the misfolding of the cellular prion protein, PrPC, into a self-templating conformer, PrPSc. Nuclear magnetic resonance (NMR) and X-ray crystallography revealed the 3D structure of the globular domain of PrPC and the possibility of its dimerization via an interchain disulfide bridge that forms due to domain swap or by non-covalent association of two monomers. On the contrary, PrPSc is composed by a complex and heterogeneous ensemble of poorly defined conformations and quaternary arrangements that are related to different patterns of neurotoxicity. Targeting PrPC with molecules that stabilize the native conformation of its globular domain emerged as a promising approach to develop anti-prion therapies. One of the advantages of this approach is employing structure-based drug discovery methods to PrPC. Thus, it is essential to expand our structural knowledge about PrPC as much as possible to aid such drug discovery efforts. In this work, we report a crystallographic structure of the globular domain of human PrPC that shows a novel dimeric form and a novel oligomeric arrangement. We use molecular dynamics simulations to explore its structural dynamics and stability and discuss potential implications of these new quaternary structures to the conversion process.

Nano-sandwich composite by kinetic trapping assembly from protein and nucleic acid.

Design and preparation of layered composite materials alternating between nucleic acids and proteins has been elusive due to limitations in occurrence and geometry of interaction sites in natural biomolecules. We report the design and kinetically controlled stepwise synthesis of a nano-sandwich composite by programmed noncovalent association of protein, DNA and RNA modules. A homo-tetramer protein core was introduced to control the self-assembly and precise positioning of two RNA–DNA hybrid nanotriangles in a co-parallel sandwich arrangement. Kinetically favored self-assembly of the circularly closed nanostructures at the protein was driven by the intrinsic fast folding ability of RNA corner modules which were added to precursor complex of DNA bound to the protein. The 3D architecture of this first synthetic protein–RNA–DNA complex was confirmed by fluorescence labeling and cryo-electron microscopy studies. The synthesis strategy for the nano-sandwich composite provides a general blueprint for controlled noncovalent assembly of complex supramolecular architectures from protein, DNA and RNA components, which expand the design repertoire for bottom-up preparation of layered biomaterials.

Dodecapeptide Cathelicidins of Cetartiodactyla: Structure, Mechanism of Antimicrobial Action, and Synergistic Interaction With Other Cathelicidins.

In this study, dodecapeptide cathelicidins were shown to be widespread antimicrobial peptides among the Cetruminantia clade. In particular, we investigated the dodecapeptide from the domestic goat Capra hircus, designated as ChDode and its unique ortholog from the sperm whale Physeter catodon (PcDode). ChDode contains two cysteine residues, while PcDode consists of two dodecapeptide building blocks and contains four cysteine residues. The recombinant analogs of the peptides were obtained by heterologous expression in Escherichia coli cells. The structures of the peptides were studied by circular dichroism (CD), FTIR, and NMR spectroscopy. It was demonstrated that PcDode adopts a β-hairpin structure in water and resembles β-hairpin antimicrobial peptides, while ChDode forms a β-structural antiparallel covalent dimer, stabilized by two intermonomer disulfide bonds. Both peptides reveal a significant right-handed twist about 200 degrees per 8 residues. In DPC micelles ChDode forms flat β-structural tetramers by antiparallel non-covalent association of the dimers. The tetramers incorporate into the micelles in transmembrane orientation. Incorporation into the micelles and dimerization significantly diminished the amplitude of backbone motions of ChDode at the picosecond-nanosecond timescale. When interacting with negatively charged membranes containing phosphatidylethanolamine (PE) and phosphatidylglycerol (PG), the ChDode peptide adopted similar oligomeric structure and was capable to form ion-conducting pores without membrane lysis. Despite modest antibacterial activity of ChDode, a considerable synergistic effect of this peptide in combination with another goat cathelicidin – the α-helical peptide ChMAP-28 was observed. This effect is based on an increase in permeability of bacterial membranes. In turn, this mechanism can lead to an increase in the efficiency of the combined action of the synergistic pair ChMAP-28 with the Pro-rich peptide mini-ChBac7.5Nα targeting the bacterial ribosome.

Intestinal Transcytosis of a Protein Cargo and Nanoparticles Mediated by a Non-Toxic Form of Pseudomonas aeruginosa Exotoxin A.

The low permeability of nanoparticles (NPs) across the intestinal epithelium remains a major challenge for their application of delivering macromolecular therapeutic agents via the oral route. Previous studies have demonstrated the epithelial transcytosis capacity of a non-toxic version of Pseudomonas aeruginosa exotoxin A (ntPE). Here, we show that ntPE can be used to deliver the protein cargo green fluorescent protein (GFP) or human growth hormone (hGH), as genetic fusions, across intact rat jejunum in a model where the material is administered by direct intra-luminal injection (ILI) in vivo in a transcytosis process that required less than 15 min. Next, ntPE chemically coupled onto biodegradable alginate/chitosan condensate nanoparticles (AC NPs-ntPE) were shown to transport similarly to ntPE-GFP and ntPE-hGH across rat jejunum. Finally, AC NPs-ntPE loaded with GFP as a model cargo were demonstrated to undergo a similar transcytosis process that resulted in GFP being colocalized with CD11c+ cells in the lamina propria after 30 min. Control NP preparations, not decorated with ntPE, were not observed within polarized epithelial cells or within the cells of the lamina propria. These studies demonstrate the capacity of ntPE to facilitate the transcytosis of a covalently associated protein cargo as well as a biodegradable NP that can undergo transcytosis across the intestinal epithelium to deliver a noncovalently associated protein cargo. In sum, these studies support the potential applications of ntPE to facilitate the oral delivery of macromolecular therapeutics under conditions of covalent or non-covalent association.

Biomimetic Recognition-Based Bioorthogonal Host–Guest Pairs for Cell Targeting and Tissue Imaging in Living Animals

Biomimetic Recognition-Based Bioorthogonal Host–Guest Pairs for Cell Targeting and Tissue Imaging in Living Animals

Block Copolymer‐Based Supramolecular Ionogels for Accurate On‐Skin Motion Monitoring

AbstractInterest in wearable and stretchable on‐skin motion sensors has grown rapidly in recent years. To expand their applicability, the sensing element must accurately detect external stimuli; however, weak adhesiveness of the sensor to a target object has been a major challenge in developing such practical and versatile devices. In this study, freestanding, stretchable, and self‐adhesive ionogel conductors are demonstrated which are composed of an associating polymer network and ionic liquid that enable conformal contact between the sensor and skin even during dynamic movement. The network of ionogel is formed by noncovalent association of two diblock copolymers, where phase‐separated micellar clusters are interconnected via hydrogen bonds between corona blocks. The resulting ionogels exhibit superior adhesive characteristics, including a very high lift‐off force of 93.3 N m−1, as well as excellent elasticity (strain at break ≈720%), toughness (≈2479 kJ m−3), thermal stability (≈150 °C), and high ionic conductivity (≈17.8 mS cm−1 at 150 °C). These adhesive ionogels are successfully applied to stretchable on‐skin strain sensors as sensing elements. The resulting devices accurately monitor the movement of body parts such as the wrist, finger, ankle, and neck while maintaining intimate contact with the skin, which was not previously possible with conventional non‐adhesive ionogels.

Noncovalent Association and Partitioning of Some Perfume Components at Infinite Dilution with Myelin Basic Protein Pseudophase in Normal Saline

Myelin basic protein (MBP), one of the major protein constituents of the myelin sheath, possesses unique ligand-binding features. We present a novel equilibrium headspace gas chromatographic technique to examine the thermodynamics of noncovalent interactions between common perfume components: Lilial, Hedione, Hexylcinnamic aldehyde, and Versalide with MBP monomers and its hexameric MBP-pseudophase. A general theoretical model is used to calculate the critical aggregation concentration (cac) of MBP, perfume component binding constants with monomeric MBP, K11, and MBP as pseudophase, Kn1, and free energies for perfume component binding with monomeric MBP, ΔGb,11, and MBP as pseudophase, ΔGb,n1. In addition, the pseudophase-water partition coefficients, Kx, the free energies of transfer of perfume from bulk water to the MBP-pseudophase, ΔGt, and the intra-aggregate activity coefficients, γm∞, at infinite dilution were also determined. The cac value measured by the method of fractional distribution is a unique and precise approach in understanding the aggregation phenomenon. Within the experimental error, the 1:1 binding free energies did not differ by more than 1 kJ/mol among the perfume components but favored the MBP pseudophase binding by 6 kJ/mol. Therefore, that protein aggregation can enhance the binding of small molecules is probably a general conclusion. While the magnitudes of K11, Kn1, ΔGb, Kx, and ΔGt show weak trends, the γm∞ values show a strong and distinct trend in interaction, spanning 4 orders of magnitude among the perfume components.

In-Vitro and In-Silico Assessment of Per- and Polyfluoroalkyl Substances (PFAS) in Aqueous Film-Forming Foam (AFFF) Binding to Human Serum Albumin.

Drinking water contaminated by fluorosurfactant-based aqueous film-forming foams (AFFF) is a source of human exposure to poly- and perfluoroalkyl substances (PFAS). However, assessment of bioaccumulation potentials of diverse PFAS in commercial products such as AFFF have been insufficient and challenging, especially due to a lack of analytical standards. Here we explore the value of suspect screening, equilibrium dialysis, and molecular-docking simulations to identify potentially bioaccumulative PFAS. We exposed human serum albumin (HSA) protein to dilutions of a legacy AFFF produced by 3M in 1999 using equilibrium dialysis and screened in-vitro protein-binding affinities using high-resolution mass spectrometry (HRMS). Through suspect screening, we identified 32 PFAS and 18 hydrocarbon surfactants in the AFFF that bound to HSA. Quantification of noncovalent association constants for 26 PFAS standards confirmed that many PFAS, including the short-chain perfluoropropane sulfonic acid (log Ka= 4.1 ± 0.2 M−1), exhibit strong binding affinities with HSA. At least five PFAS in AFFF (including three PFAS with less than five perfluorocarbons) remained bound to the precipitated HSA pellet after extensive solvent washing—an indication of high PFAS binding potential. Three PFAS (PFBS, PFOS, and PFOA) were confirmed in the protein pellet with analytical standards and quantified after acid digestion—this sample fraction accounted for 5 to 20% of each compound mass in the sample. We calculated pseudo-bioconcentration factors (BCFpseudo) for PFAS that suspect screening flagged as noncovalently bound or potentially covalently bound. Most PFAS exhibiting high BCFpseudo, especially those with seven perfluorocarbons, contained a carboxylic acid or a sulfonic acid. Finally, we used molecular docking to simulate HSA binding affinities for 62 ligands (26 PFAS targets, 18 PFAS qualified in AFFF, and 18 hydrocarbon surfactants qualified in AFFF). We found that molecular docking can effectively separate HSA-binding and -nonbinding compounds in AFFF. In-vitro and in-silico approaches described in this study provide replicable, high-throughput workflows for assessing bioaccumulation potentials of diverse PFAS in commercial products.

How the Discovery of the CD4/CD8-p56lck Complexes Changed Immunology and Immunotherapy.

The past 25 years have seen enormous progress in uncovering the receptors and signaling mechanisms on T-cells that activate their various effecter functions. Until the late 1980s, most studies on T-cells had focused on the influx of calcium and the levels of cAMP/GMP in T-cells. My laboratory then uncovered the interaction of CD4 and CD8 co-receptors with the protein-tyrosine kinase p56lck which are now widely accepted as the initiators of the tyrosine phosphorylation cascade leading to T-cell activation. The finding explained how immune recognition receptors expressed by many immune cells, which lack intrinsic catalytic activity, can transduce activation signals via non-covalent association with non-receptor tyrosine kinases. The discovery also established the concept that a protein tyrosine phosphorylation cascade operated in T-cells. In this vein, we and others then showed that the CD4- and CD8-p56lck complexes phosphorylate the TCR complexes which led to the identification of other protein-tyrosine kinases such as ZAP-70 and an array of substrates that are now central to studies in T-cell immunity. Other receptors such as B-cell receptor, Fc receptors and others were also subsequently found to use src kinases to control cell growth. In T-cells, p56lck driven phosphorylation targets include co-receptors such as CD28 and CTLA-4 and immune cell-specific adaptor proteins such as LAT and SLP-76 which act to integrate signals proximal to surface receptors. CD4/CD8-p56lck regulated events in T-cells include intracellular calcium mobilization, integrin activation and the induction of transcription factors for gene expression. Lastly, the identification of the targets of p56lck in the TCR and CD28 provided the framework for the development of chimeric antigen receptor (CAR) therapy in the treatment of cancer. In this review, I outline a history of the development of events that led to the development of the “TCR signaling paradigm” and its implications to immunology and immunotherapy.

Crystal structure of five solid forms from isonicotinamide and carboxylic acids assembled by classical hydrogen bonds and other noncovalent interactions

Cocrystallization of the commonly available isonicotinamide, with a series of carboxylic acids gave a total of five new anhydrous and hydrous multicomponent solid forms: (isonicotinamide)2: (suberic acid) [(L)2 · (H2sub), H2sub = suberic acid] (1), (isonicotinamide)2: (α-ketoglutaric acid): H2O [(HL+)2 · (kga2−) · H2O, kga2− = α-ketoglutarate] (2), (isonicotinamide): (1,2-phenylenediacetic acid) [(L) · (H2pda), H2pda = 1,2-phenylenediacetic acid] (3), (isonicotinamide): (4-nitrophthalic acid) [(HL+) · (Hnpta−), Hnpta− = 4-nitrohydrogenphthalate] (4) and (isonicotinamide)4: (butane-1,2,3,4-tetracarboxylic acid) [(L)4 · (H4bta), H4bta = butane-1,2,3,4-tetracarboxylic acid] (5). The five solid forms have been characterised by XRD, IR and EA and their melting points were also reported. Their structural and supramolecular aspects are fully analyzed.The result shows that 2 and 4 are organic salts with only the aryl N in L protonated, 1, 3 and 5 are co-crystals. The crystal packing is interpreted by the strong N-H···O, O-H···N and O-H···O hydrogen bonds. The carboxamide dimers were existed in all solid forms by a pair of N-H···O hydrogen bonds. Further inspection of the crystal packing told that a different set of additional CH-O/CH2-O, CH-N, O-C, O-O, O-N, O-π and π-π associations contribute to the stabilization and expansion of the total high-dimensional (2D-3D) structures. For the delicate balance of the various weak nonbonding interactions these structures adopted homo/hetero supramolecular synthons or both and the common R21(7) and R22(8) graph sets have been observed in all solid forms due to the interplay of hydrogen bonds and non-covalent associations.

Peptide-Tetrapyrrole Supramolecular Self-Assemblies: State of the Art.

The covalent and noncovalent association of self-assembling peptides and tetrapyrroles was explored as a way to generate systems that mimic Nature’s functional supramolecular structures. Different types of peptides spontaneously assemble with porphyrins, phthalocyanines, or corroles to give long-range ordered architectures, whose structure is determined by the features of both components. The regular morphology and ordered molecular arrangement of these systems enhance the photochemical properties of embedded chromophores, allowing applications as photo-catalysts, antennas for dye-sensitized solar cells, biosensors, and agents for light-triggered therapies. Chemical modifications of peptide and tetrapyrrole structures and control over the assembly process can steer the organization and influence the properties of the resulting system. Here we provide a review of the field, focusing on the assemblies obtained from different classes of self-assembling peptides with tetrapyrroles, their morphologies and their applications as innovative functional materials.

Eight salts of 4-dimethylaminopyridine and organic acids by H-bonds and some noncovalent associations

This article reports the 4-dimethylaminopyridine based supramolecular crystalline solids 1-8, where the organic acids have been integrated. Addition of the 4-dimethylaminopyridine to the solution of organic acid makes the corresponding supramolecular assemblies. All the compounds crystallize as the corresponding salts and they have been featured in detail via IR, mp, EA and XRD. The major driving force is the classical H-bonds from 4-dimethylaminopyridine and the acids. Further analysis of the crystal packing of the salts told that a different array of additional CH-C, CH-O/CH3-O, CH-π/CH3-π, CH-CH, CH-Cl/CH3-Cl, OH-π, O-C, O-N, O-O, O-π and Cl-O contacts contribute to the stabilization and expansion of the total 1D-3D structures. For the delicate balance of the various weak nonbonding interactions, these structures adopted homo or hetero supramolecular synthons or both.

Probing sulfatide-tissue lectin recognition with functionalized glycodendrimersomes.

SummaryThe small 3-O-sulfated galactose head group of sulfatides, an abundant glycosphingolipid class, poses the (sphinx-like) riddle on involvement of glycan bridging by tissue lectins (sugar code). First, synthesis of head group derivatives for functionalization of amphiphilic dendrimers is performed. Aggregation of resulting (biomimetic) vesicles, alone or in combination with lactose, demonstrates bridging by a tissue lectin (galectin-4). Physiologically, this can stabilize glycolipid-rich microdomains (rafts) and associate sulfatide-rich regions with specific glycoproteins. Further testing documents importance of heterobivalency and linker length. Structurally, sulfatide recognition by galectin-8 is shown to involve sphingosine's OH group as substitute for the 3′-hydroxyl of glucose of lactose. These discoveries underscore functionality of this small determinant on biomembranes intracellularly and on the cell surface. Moreover, they provide a role model to examine counterreceptor capacity of more complex glycans of glycosphingolipids and to start their bottom-up glycotope surface programming.

Scalable fabrication of carbon materials based silicon rubber for highly stretchable e-textile sensor

Abstract Development of stretchable wearable devices requires essential materials with high level of mechanical and electrical properties as well as scalability. Recently, silicone rubber-based elastic polymers with incorporated conductive fillers (metal particles, carbon nanomaterials, etc.) have been shown to the most promising materials for enabling both high electrical performance and stretchability, but the technology to make materials in scalable fabrication is still lacking. Here, we propose a facile method for fabricating a wearable device by directly coating essential electrical material on fabrics. The optimized material is implemented by the noncovalent association of multiwalled carbon nanotube (MWCNT), carbon black (CB), and silicon rubber (SR). The e-textile sensor has the highest gauge factor (GF) up to 34.38 when subjected to 40% strain for 5,000 cycles, without any degradation. In particular, the fabric sensor is fully operational even after being immersed in water for 10 days or stirred at room temperature for 8 hours. Our study provides a general platform for incorporating other stretchable elastic materials, enabling the future development of the smart clothing manufacturing.