Diastereodivergent synthesis of multi-substituted cycloalkanes.

The escape from flat aromatic architectures towards saturated structures enriched with an increased proportion of sp atoms (Fsp) has been harnessed as a drug design strategy. Chemical synthesis of drug-like saturated cycloalkanes, particularly in terms of the precise control of substituents either on the same or opposing faces of the ring plane, poses greater complexities than the assembly of their two-dimensional aromatic analogues. Reliable and predictable divergent synthesis of all isomers of multi-substituted cycloalkanes continues to pose a formidable challenge.

Synthesis of deuterated acids and bases using bipolar membranes.

Deuterated acids/bases are high-value bulk chemicals used for synthesizing deuterated pharmaceuticals, modifying optoelectronic materials and mediating hydrogen isotope exchange reactions. However, conventional synthesis methods require harsh reaction conditions with high energy consumption. Here we propose a versatile platform that takes advantage of heavy water dissociation in bipolar membranes (BPMs) to produce deuterated acids and bases under particularly mild conditions.

Edge-feeding synchronous epitaxy of layer-controlled graphene films on heterogeneous catalytic substrates.

Compared with single-layer two-dimensional (2D) materials, bilayer, trilayer, and few-layer 2D materials exhibit enhanced band structure tunability, improved electrical and thermal properties, and superior mechanical strength and barrier performance. However, the layer-controlled synthesis of 2D films with high layer number uniformity remains challenging, due to the difficulty in the additional layer nucleation and the effective realization of layer-by-layer growth. Herein, we report an edge-feeding synchronous epitaxial growth mode breaking the limit of traditional epitaxy theories.

Assignment of Disulfide Bonds in HNTX-XXI by Double-Enzymatic Digestion and Edman Degradation.

HNTX-XXI, a peptide toxin derived from the venom of the spider , comprises a 64-amino-acid protein architecture that notably incorporates eight cysteine residues positioned at positions 2, 10, 14, 16, 17, 23, 36, and 63. The close spatial proximity of Cys16 and Cys17 poses a challenge in resolving their disulfide bridge configurations using standard methodologies. In this study, we introduce an innovative and highly efficient approach for delineating disulfide pairings in peptides containing adjacent cysteines.

Molecular mechanisms of two novel and selective TRPV1 channel activators.

Venomous toxins hold immense value as tools in elucidating the intricate structure and underlying mechanisms of ion channels. In this article, we identified of two novel toxins, Hainantoxin-XXI (HNTX-XXI) and Hainantoxin-XXII (HNTX-XXII), derived from the venom of the Chinese spider Ornithoctonus hainana. HNTX-XXI, boasting a molecular weight of 6869.

Quantum Neural Network Inspired Hardware Adaptable Ansatz for Efficient Quantum Simulation of Chemical Systems.

The variational quantum eigensolver is a promising way to solve the Schrödinger equation on a noisy intermediate-scale quantum (NISQ) computer, while its success relies on a well-designed wave function ansatz. Inspired by the quantum neural network, we propose a new hardware heuristic ansatz where its expressibility can be improved by increasing either the depth or the width of the circuit. Such a character makes this ansatz adaptable to different hardware environments.

Molecular mechanism by which spider-driving peptide potentiates coagulation factors.

Hemostasis is a crucial process that quickly forms clots at injury sites to prevent bleeding and infections. Dysfunctions in this process can lead to hemorrhagic disorders, such as hemophilia and thrombocytopenia purpura. While hemostatic agents are used in clinical treatments, there is still limited knowledge about potentiators targeting coagulation factors.

Exploring Accurate Potential Energy Surfaces via Integrating Variational Quantum Eigensolver with Machine Learning.

The potential energy surface (PES) is crucial for interpreting a variety of chemical reaction processes. However, predicting accurate PESs with high-level electronic structure methods is a challenging task due to the high computational cost. As an appealing application of quantum computing, we show in this work that variational quantum algorithms can be integrated with machine learning (ML) techniques as a promising scheme for exploring accurate PESs.

Effects of JZTX-V on the wild type Kv4.3 Expressed in HEK293T and Molecular Determinants in the Voltage-sensing Domains of Kv4.3 Interacting with JZTX-V.

JZTX-V is a toxin isolated from the venom of the Chinese spider . Previous studies had shown that JZTX-V could inhibit the transient outward potassium current of Kv4.2 and Kv4.

Understanding High-Temperature Chemical Reactions on Metal Surfaces: A Case Study on Equilibrium Concentration and Diffusivity of C H on a Cu(111) Surface.

Chemical reactions on metal surfaces are important in various processes such as heterogeneous catalysis and nanostructure growth. At moderate or lower temperatures, these reactions generally follow the minimum energy path, and temperature effects can be reasonably described by a harmonic oscillator model. At a high temperature approaching the melting point of the substrate, general behaviors of surface reactions remain elusive.

Toward Epitaxial Growth of Misorientation-Free Graphene on Cu(111) Foils.

The epitaxial growth of single-crystal thin films relies on the availability of a single-crystal substrate and a strong interaction between epilayer and substrate. Previous studies have reported the roles of the substrate (..

JZTX-V Targets the Voltage Sensor in Kv4.2 to Inhibit I Potassium Channels in Cardiomyocytes.

Kv4 potassium channels are responsible for transient outward K currents in the cardiac action potential (AP). Previous experiments by our group demonstrated that Jingzhaotoxin-V (JZTX-V) selectively inhibits A-type potassium channels. However, the specific effects of JZTX-V on the transient outward (I) current of cardiomyocytes and underlying mechanism of action remain unclear.

The Venom of Ornithoctonus huwena affect the electrophysiological stability of neonatal rat ventricular myocytes by inhibiting sodium, potassium and calcium current.

Spider venoms are known to contain various toxins that are used as an effective means to capture their prey or to defend themselves against predators. An investigation of the properties of Ornithoctonus huwena (O.huwena) crude venom found that the venom can block neuromuscular transmission of isolated mouse phrenic nerve-diaphragm and sciatic nerve-sartorius preparations.

Selective Closed-State Nav1.7 Blocker JZTX-34 Exhibits Analgesic Effects against Pain.

Jingzhaotoxin-34 (JZTX-34) is a selective inhibitor of tetrodotoxin-sensitive (TTX-S) sodium channels. In this study, we found that JZTX-34 selectively acted on Nav1.7 with little effect on other sodium channel subtypes including Nav1.

Molecular determinant for the tarantula toxin Jingzhaotoxin-I slowing the fast inactivation of voltage-gated sodium channels.

Peptide toxins often have divergent pharmacological functions and are powerful tools for a deep review on the current understanding of the structure-function relationships of voltage-gated sodium channels (VGSCs). However, knowing about the interaction of site 3 toxins from tarantula venoms with VGSCs is not sufficient. In the present study, using whole-cell patch clamp technique, we determined the effects of Jingzhaotoxin-I (JZTX-I) on five VGSC subtypes expressed in HEK293 cells.

Structural and Functional Diversity of Peptide Toxins from Tarantula Haplopelma hainanum (Ornithoctonus hainana) Venom Revealed by Transcriptomic, Peptidomic, and Patch Clamp Approaches.

Spider venom is a complex mixture of bioactive peptides to subdue their prey. Early estimates suggested that over 400 venom peptides are produced per species. In order to investigate the mechanisms responsible for this impressive diversity, transcriptomics based on second generation high throughput sequencing was combined with peptidomic assays to characterize the venom of the tarantula Haplopelma hainanum.

The activation effect of hainantoxin-I, a peptide toxin from the Chinese spider, Ornithoctonus hainana, on intermediate-conductance Ca2+-activated K+ channels.

Intermediate-conductance Ca2+-activated K+ (IK) channels are calcium/calmodulin-regulated voltage-independent K+ channels. Activation of IK currents is important in vessel and respiratory tissues, rendering the channels potential drug targets. A variety of small organic molecules have been synthesized and found to be potent activators of IK channels.

Molecular surface of JZTX-V (β-Theraphotoxin-Cj2a) interacting with voltage-gated sodium channel subtype NaV1.4.

Voltage-gated sodium channels (VGSCs; NaV1.1-NaV1.9) have been proven to be critical in controlling the function of excitable cells, and human genetic evidence shows that aberrant function of these channels causes channelopathies, including epilepsy, arrhythmia, paralytic myotonia, and pain.

Toxin diversity revealed by a transcriptomic study of Ornithoctonus huwena.

Spider venom comprises a mixture of compounds with diverse biological activities, which are used to capture prey and defend against predators. The peptide components bind a broad range of cellular targets with high affinity and selectivity, and appear to have remarkable structural diversity. Although spider venoms have been intensively investigated over the past few decades, venomic strategies to date have generally focused on high-abundance peptides.

Effects of the venom of the spider Ornithoctonus hainana on neonatal rat ventricular myocytes cellular and ionic electrophysiology.

Cardiac ion channels are membrane-spanning proteins that allow the passive movement of ions across the cell membrane along its electrochemical gradient, which regulates the resting membrane potential as well as the shape and duration of the cardiac action potential. Additionally, they have been recognized as potential targets for the actions of neurotransmitters, hormones and drugs of cardiac diseases. Spider venoms contain high abundant of toxins that target diverse ion channels and have been considered as a potential resource of new constituents with specific pharmacological properties.

Proteomic analysis of the venom from the scorpion Mesobuthus martensii.

Unlabelled: The scorpion Mesobuthus martensii is the most populous species in eastern Asian countries, and several toxic components have been identified from their venoms. Nevertheless, a complete proteomic profile of the venom of M. martensii is still not available.

Screening for voltage-gated sodium channel interacting peptides.

The voltage-gated sodium channel (VGSC) interacting peptide is of special interest for both basic research and pharmaceutical purposes. In this study, we established a yeast-two-hybrid based strategy to detect the interaction(s) between neurotoxic peptide and the extracellular region of VGSC. Using a previously reported neurotoxin JZTX-III as a model molecule, we demonstrated that the interactions between JZTX-III and the extracellular regions of its target hNav1.

Huwentoxin-XVI, an analgesic, highly reversible mammalian N-type calcium channel antagonist from Chinese tarantula Ornithoctonus huwena.

N-type calcium channels play important roles in the control of neurotransmission release and transmission of pain signals to the central nervous system. Their selective inhibitors are believed to be potential drugs for treating chronic pain. In this study, a novel neurotoxin named Huwentoxin-XVI (HWTX-XVI) specific for N-type calcium channels was purified and characterized from the venom of Chinese tarantula Ornithoctonus huwena.

[Synthesis, refolding and identification of pharmacological activities of neurotoxin JZTX-XI and R3A-JZTX-XI].

Kv2.1 channel currents in pancreatic beta-cells are thought to contribute to action potential repolarization and thereby modulate insulin secretion. Because of its central role in this important physiological process, Kv2.