Tweezer-type binding cavity formed by the helical folding of a carbazole–pyridine oligomer

We have synthesised a new aromatic foldamer based on the carbazole–pyridine oligomers that adopt helical conformations via dipole-dipole interactions and π-stacking between two ethynyl bond-linked monomers. This foldamer scaffold has...

Effect of a cis-4-Aminopiperidine-3-carboxylic Acid (cis-APiC) Residue on Mixed-helical Folding of Unnatural Peptides

The α/β-peptide 11/9-helix and the β-peptide 12/10-helix belong to “mixed” helices, in which two types of hydrogen bonds with opposite directionality alternate along the helical axis. cis-2-Aminocyclohaxanecarboxylic acid (cis-ACHC) is...

Constructing synthetic-protein assemblies from de novo designed 310 helices

Compared with the iconic α helix, 310 helices occur much less frequently in protein structures. The different 310-helical parameters lead to energetically less favourable internal energies, and a reduced tendency to pack into defined higher-order structures. Consequently, in natural proteins, 310 helices rarely extend past 6 residues, and do not form regular supersecondary, tertiary, or quaternary interactions. Here, we show that despite their absence in nature, synthetic protein-like assemblies can be built from 310 helices. We report the rational design, solution-phase characterisation, and an X-ray crystal structure for water-soluble bundles of 310 helices with consolidated hydrophobic cores. The design uses 6-residue repeats informed by analysing natural 310 helices, and incorporates aminoisobutyric acid residues. Design iterations reveal a tipping point between α-helical and 310-helical folding, and identify features required for stabilising assemblies in this unexplored region of protein-structure space.

Dual effects of presynaptic membrane mimetics on α-synuclein amyloid aggregation

Aggregation of intrinsically disordered α-synuclein (αSN) under various conditions is closely related to synucleinopathies. Although various biological membranes have shown to alter the structure and aggregation propensity of αSN, a thorough understanding of the molecular and mechanical mechanism of amyloidogenesis in membranes remains unanswered. Herein, we examined the structural changes, binding properties, and amyloidogenicity of three variations of αSN mutants under two types of liposomes, 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and presynaptic vesicle mimetic (Mimic) membranes. While neutrally charged DOPC membranes elicited marginal changes in the structure and amyloid fibrillation of αSNs, negatively charged Mimic membranes induced dramatic helical folding and biphasic amyloid generation. At low concentration of Mimic membranes, the amyloid fibrillation of αSNs was promoted in a dose-dependent manner. However, further increases in the concentration constrained the fibrillation process. These results suggest the dual effect of Mimic membranes on regulating the amyloidogenesis of αSN, which is rationalized by the amyloidogenic structure of αSN and condensation-dilution of local αSN concentration. Finally, we propose physicochemical properties of αSN and membrane surfaces, and their propensity to drive electrostatic interactions as decisive factors of amyloidogenesis.

Human ACE2 peptide-mimics block SARS-CoV-2 pulmonary cells infection

In light of the recent accumulated knowledge on SARS-CoV-2 and its mode of human cells invasion, the binding of viral spike glycoprotein to human Angiotensin Converting Enzyme 2 (hACE2) receptor plays a central role in cell entry. We designed a series of peptides mimicking the N-terminal helix of hACE2 protein which contains most of the contacting residues at the binding site, exhibiting a high helical folding propensity in aqueous solution. Our best peptide-mimics are able to block SARS-CoV-2 human pulmonary cell infection with an inhibitory concentration (IC50) in the nanomolar range upon binding to the virus spike protein with high affinity. These first-in-class blocking peptide mimics represent powerful tools that might be used in prophylactic and therapeutic approaches to fight the coronavirus disease 2019 (COVID-19).

Chiral Nanotubes Self-Assembled from Discrete Non-Covalent Macrocycles

Many strategies have been used to construct supramolecular hollow tubes, including helical folding of oligomers, bundling of rod-like structures, rolling-up of sheets and stacking of covalent cycles. On the other...

Identification and Physicochemical Characterization of a New Allergen from Ascaris lumbricoides

To analyze the impact of Ascaris lumbricoides infection on the pathogenesis and diagnosis of allergic diseases, new allergens should be identified. We report the identification of a new Ascaris lumbricoides allergen, Asc l 5. The aim of this study was to evaluate the physicochemical and immunological features of the Asc l 5 allergen. We constructed an A. lumbricoides cDNA library and Asc l 5 was identified by immunoscreening. After purification, rAsc l 5 was physicochemically characterized. Evaluation of its allergenic activity included determination of Immunoglobulin E (IgE) binding frequency (in two populations: 254 children and 298 all-age subjects), CD203c based-basophil activation tests (BAT) and a passive cutaneous anaphylaxis (PCA) mouse model. We found by amino acid sequence analysis that Asc l 5 belongs to the SXP/RAL-2 protein family of nematodes. rAsc l 5 is a monomeric protein with an alpha-helical folding. IgE sensitization to rAsc l 5 was around 52% in general population; positive BAT rate was 60%. rAsc l 5 induced specific IgE production in mice and a positive PCA reaction. These results show that Asc l 5 has structural and immunological characteristics to be considered as a new allergen from A. lumbricoides.

Synthesis and Optical Properties of Triphenylene-Based Donor-Donor and Donor-Acceptor Conjugated Polymers: A Comparative Study

Two new conjugated polymers (P1 and P2), containing a bithiophene donor unit coupled with either a triphenylene donor unit or an imide-functionalized triphenylene acceptor unit in the backbone, have been synthesized, structurally characterized, and comparatively studied by using 1H NMR, FT-IR, gel permeation chromatography, differential scanning calorimetry, cyclic voltammetry, ultraviolet-visible absorption, and fluorescence spectroscopy. Both polymers are amorphous in nature and thermally stable up to 450°C. The inclusion of the imide functionalization in the triphenylene unit significantly lowered the lowest unoccupied molecular orbital energy level and thus the bandgap of the donor-acceptor polymer P2 over the donor-donor polymer P1. P1 and P2 show very different optical properties in hexane and other solvents. P1 shows a broad emission in hexane but vibronically structured emissions in other solvents; in contrast, P2 exhibits a vibronically resolved emission in hexane, while exhibiting redshifted, broad, and featureless emissions in other solvents. P1 takes a random coil conformation in good solvents like p-xylene, benzene, toluene, anisole, chloroform, THF, and o-dichlorobenzene, whereas in hexane, it may adopt a helical folding conformation. In the poor solvent DMSO, interchain aggregates dominate. P2, on the other hand, adopts a random coil conformation in hexane but possibly the helical folding conformation in other good solvents. The opposite conformations of the two polymers may be responsible for their opposite solvent-dependent fluorescence properties. By virtue of the very different fluorescence properties of these two polymers in nonpolar solvents such as hexane and in polar solvents, the potential of using the polymers to detect the trace amount of ethanol content that is added to gasoline has been revealed with high sensitivity.