Developing a fast and catalyst-free protocol to form C=N double bond with high functional group tolerance.

The carbon-nitrogen double bond (C=N) is a fundamentally important functional group in organic chemistry. This is largely due to the fact that C=N acts as electrophilic synthon to give nitrogen-containing compounds. Here, we report the condensation of primary amine or hydrazine with very electron-deficient aldehyde to form C=N bond in the absence of any catalysts (metals and acids).

Lysosomal K channel TMEM175 promotes apoptosis and aggravates symptoms of Parkinson's disease.

Lysosomes are degradative organelles and play vital roles in a variety of cellular processes. Ion channels on the lysosomal membrane are key regulators of lysosomal function. TMEM175 has been identified as a lysosomal potassium channel, but its modulation and physiological functions remain unclear.

Genetically encoded FRET fluorescent sensor designed for detecting MOF histone acetyltransferase activity in vitro and in living cells.

Acetylation of lysine in the histone H4 N-terminal is one of the most significant epigenetic modifications in cells. Aberrant changes involving lysine acetylation modification are commonly reported in multiple types of cancers. Currently, whether it is for in vivo or in vitro, there are limited approaches for the detection of H4 lysine acetylation levels.

Feedback control of PLK1 by Apolo1 ensures accurate chromosome segregation.

Stable transmission of genetic material during cell division requires accurate chromosome segregation. PLK1 dynamics at kinetochores control establishment of correct kinetochore-microtubule attachments and subsequent silencing of the spindle checkpoint. However, the regulatory mechanism responsible for PLK1 activity in prometaphase has not yet been affirmatively identified.

Highly selective fluorescence probe with peptide backbone for imaging mercury ions in living cells based on aggregation-induced emission effect.

Mercury is an anthropogenic toxic heavy metal found in the environment. It is highly desirable to develop a fluorescence probe that can selectively and sensitively detect mercury ions using a turn-on response. This paper reports the successful development of a peptide fluorescence probe, TP-2 (TPE-Trp-Pro-Gln-His-Glu-NH), which uses aggregation-induced emission effects and high selectivity to detect Hg.

Specific epitopes form extensive hydrogen-bonding networks to ensure efficient antibody binding of SARS-CoV-2: Implications for advanced antibody design.

Neutralizing antibody targeting to the SARS-CoV-2 could provide powerful therapies. A neutralizing antibody CC12.1 which was found in SARS-CoV-2 patient samples provides potential protection from disease.

Novel gene-encoded intermolecular FRET sensor for tracking glycosylation of CD147 in living cells.

CD147 is involved in various physiological processes and plays important roles for tumor metastasis. Glycosylation of the protein determines numerous functions of CD147. Up to now, hardly any sensor has been developed for detecting glycosylation of CD147 in live cells.

Design, synthesis and cell imaging of a simple peptide-based probe for the selective detection of RNA.

Here we present a novel peptide-based fluorescent "turn-on" molecule P1 for detecting RNA, in a double or single strand, AU-rich or CG-rich. Both computational and experimental studies indicate that the detection efficiency depends on the binding affinity of P1 and conformational changes. P1 could be applied for cell imaging without any additional transfection vectors.

Discovery and Biological Evaluation of CD147 -Glycan Inhibitors: A New Direction in the Treatment of Tumor Metastasis.

-glycosylation is instrumental to the regulation of CD147 functions, including the maturation of CD147, secretion of matrix metalloproteinases (MMPs), and promotion of tumor metastasis. Glycosylated CD147 is highly expressed in various cancer types, participates in metastasis, and is associated with the poor prognosis of malignant tumors. However, to date, there has been little development of target-specific inhibitors for CD147 glycosylation.

Repurposing Low-Molecular-Weight Drugs against the Main Protease of Severe Acute Respiratory Syndrome Coronavirus 2.

The coronavirus disease pandemic caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected the global healthcare system. As low-molecular-weight drugs have high potential to completely match interactions with essential SARS-CoV-2 targets, we propose a strategy to identify such drugs using the fragment-based approach. Herein, using ligand- and protein-observed fragment screening approaches, we identified niacin and hit binding to the catalytic pocket of the main protease (M) of SARS-CoV-2, thereby modestly inhibiting the enzymatic activity of M.

Cannabinoids Rescue Cocaine-Induced Seizures by Restoring Brain Glycine Receptor Dysfunction.

Cannabinoids are reported to rescue cocaine-induced seizures (CISs), a severe complication in cocaine users. However, the molecular targets for cannabinoid therapy of CISs remain unclear. Here, we report that the systemic administration of cannabinoids alleviates CISs in a CB/CB-receptor-independent manner.

A peptide-based fluorescent sensor for selective imaging of glutathione in living cells and zebrafish.

Monitoring and imaging glutathione (GSH) in living systems is an essential tool to determine the key roles of GSH in biological pathways, but most fluorescent sensors can only be used in vitro because of their potential biotoxicity. Here, a peptide-based fluorescent sensor, FP, has been successfully designed and synthesized based on the biocompatibility of the peptide backbone and low toxicity. The design strategy of FP contains a specific spatial structure of the peptide sequence which selectively binds to Cu, triggering fluorescence quenching.

Human Hyperekplexic Mutations in Glycine Receptors Disinhibit the Brainstem by Hijacking GABA Receptors.

Hyperekplexia disease is usually caused by naturally occurring point mutations in glycine receptors (GlyRs). However, the γ-aminobutyric acid type A receptor (GABAR) seems to be also involved regarding the therapeutic basis for hyperekplexia using benzodiazepines, which target GABARs but not GlyRs. Here, we show that the function of GABARs was significantly impaired in the hypoglossal nucleus of hyperekplexic transgenic mice.

Identification of the hot spot residues for pyridine derivative inhibitor CCT251455 and ATP substrate binding on monopolar spindle 1 (MPS1) kinase by molecular dynamic simulation.

Protein kinase monopolar spindle 1 plays an important role in spindle assembly checkpoint at the onset of mitosis. Over expression of MPS1 correlated with a wide range of human tumors makes it an attractive target for finding an effective and specific inhibitor. In this work, we performed molecular dynamics simulations of protein MPS1 itself as well as protein bound systems with the inhibitor and natural substrate based on crystal structures.

Identification of the quinolinedione inhibitor binding site in Cdc25 phosphatase B through docking and molecular dynamics simulations.

Cdc25 phosphatase B, a potential target for cancer therapy, is inhibited by a series of quinones. The binding site and mode of quinone inhibitors to Cdc25B remains unclear, whereas this information is important for structure-based drug design. We investigated the potential binding site of NSC663284 [DA3003-1 or 6-chloro-7-(2-morpholin-4-yl-ethylamino)-quinoline-5, 8-dione] through docking and molecular dynamics simulations.

Discovery of Cdc25A Lead Inhibitors with a Novel Chemotype by Virtual Screening: Application of Pharmacophore Modeling Based on a Training Set with a Limited Number of Unique Components.

Cdc25 phosphatase was studied as an attractive target for cancer therapy. Multiple pharmacophore models with the unique core features of classic quinone inhibitors and those of novel inhibitors were used to discover a novel lead inhibitor. A total of 21 compounds with qualified physical properties were screened from the Maybridge HitFinder database containing 14 400 compounds by pharmacophore models.

Identification of Binding Modes for Amino Naphthalene 2-Cyanoacrylate (ANCA) Probes to Amyloid Fibrils from Molecular Dynamics Simulations.

The amino naphthalene 2-cyanoacrylate (ANCA) probe is a kind of fluorescent amyloid binding probe that can report different fluorescence emissions when bound to various amyloid deposits in tissue, while their interactions with amyloid fibrils remain unclear due to the insoluble nature of amyloid fibrils. Here, all-atom molecular dynamics simulations were used to investigate the interaction between ANCA probes with three different amyloid fibrils. Two common binding modes of ANCA probes on Aβ40 amyloid fibrils were identified by cluster analysis of multiple simulations.

A novel peptide-based fluorescence chemosensor for selective imaging of hydrogen sulfide both in living cells and zebrafish.

Hydrogen sulfide (HS) plays an important role as a signaling compound (gasotransmitter) in living systems. However, the development of an efficient imaging chemosensor of HS in live animals is a challenging field for chemists. Herein, a novel peptide-based fluorescence chemosensor L-Cu was designed and synthesized on the basis of the copper chelating with the peptide ligand (FITC-Ahx-Ser-Pro-Gly-His-NH, L), and its HS sensing ability has been evaluated both in living cells and zebrafish.

Fluorescence "on-off-on" peptide-based chemosensor for the selective detection of Cu and S and its application in living cell bioimaging.

Copper ions are known to be very important for homeostasis, which is critical for the metabolism and development of living organisms. In addition, sulfide ions, as an important endogenously produced gasotransmitter, have been proved to be implicated in a variety of physiological functions such as anti-apoptosis, vasodilation, antioxidation, and anti-inflammation. Herein, we report the development of a novel fluorescence chemosensor (L) based on a tetra-peptide conjugated with dansyl groups as a promising analytical tool for detecting Cu and S in 100% aqueous solutions, which exhibits excellent cell biotoxicity and intracellular biosensing ability.

Highly selective ratiometric peptide-based chemosensors for zinc ions and applications in living cell imaging: a study for reasonable structure design.

Recently, fluorescent peptide-based chemosensors have been reported and used to detect series of metal ions in both aqueous solutions and living cells. In order to explore and indicate the structural regulations of "fluorophore-(His)-Pro-Gly-(His)-fluorophore (HL peptide sensor)", we predict the relationship between the number of histidine molecules and the coordination activity, as well as the preferred coordination site, through computational studies. L was modeled as showing the highest activity with the lowest calculated ΔE, and inner histidine residues bonding with the "Pro-Gly" core structure always provided essential coordination sites for zinc ions.

A novel fluorescent chemosensor based on tetra-peptides for detecting zinc ions in aqueous solutions and live cells.

A fluorescent chemosensor is a powerful analytical tool for the visualization and quantitation of analytes in living cells, tissue slices, and whole bodies. Peptides with a reporter ionophore are very valuable as fluorescent chemosensors, because of their higher biological compatibility and solubility compared to organic dyes, and they are more stable than proteins in aqueous solutions. Herein, we report a novel peptide fluorescent chemosensor (HL) based on tetra-peptides conjugated with dansyl groups, which was synthesized by solid phase peptide synthesis.

A peptide-based fluorescent chemosensor for measuring cadmium ions in aqueous solutions and live cells.

A novel peptide fluorescent chemosensor (H2L) with a lysine backbone and both -NH2 sites conjugated with cysteine and dansyl groups has been designed and synthesized by solid phase peptide synthesis with Fmoc chemistry. This chemosensor is a promising analytical tool for detecting Cd(2+) based on the photo-induced electron transfer (PET) effect by turn-on response in 100% aqueous solutions. As designed, H2L exhibits excellent cell permeation and low biotoxicity as well as displaying relatively high selectivity and sensitivity.

Spectroscopic and Microscopic Studies on the Mechanism of Mitochondrial Toxicity Induced by CdTe QDs Modified with Different Ligands.

Quantum dots (QDs) are increasingly applied in sensing, drug delivery, biomedical imaging, electronics industries, etc. Consequently, it is urgently required to examine their potential threat to humans and the environment. In the present work, the toxicity of CdTe QDs with nearly identical maximum emission wavelength but modified with two different ligands (MPA and BSA) to mitochondria was investigated using flow cytometry, spectroscopic, and microscopic methods.

Multi-spectroscopic analysis and molecular modeling on the interaction of curcumin and its derivatives with human serum albumin: a comparative study.

The comparative study about the interaction between curcumin and its derivatives (demothxycurcumin and bisdeoxycurcumin) with human serum albumin (HSA) has been carried out using multi-spectroscopic analysis and molecular modeling method. The characteristic of fluorescence quenching and the thermodynamic parameters have been studied by state emission fluorescence experiments under different temperatures with an interval of 6 K. Curcumin shows largest quenching constant and bisdeoxycurcumin shows the smallest at the temperature of 298 K.