Ligands and binding

TIGIT is an inhibitory receptor on immune cells that outcompetes an activating receptor, CD226, for shared ligands. Tumor-infiltrating lymphocytes express TIGIT and CD226 on regulatory T cells (Treg) and on CD8+ T cells with tumor-reactive or exhausted phenotypes, supporting the potential of therapeutically targeting TIGIT to enhance anti-tumor immunity. To optimize the efficacy of therapeutic antibodies against TIGIT, it is necessary to understand whether there is therapeutic benefit from Fcγ receptor (FcγR) binding...

In this study, several imidazole derivatives in one pot multicomponent reaction from various aldehydes (1(a-z)), 9,10-phenanthrenequinone, or benzyl (2), and ammonium acetate (3) were synthesized in the presence of acetic acid (AcOH) under reflux conditions at 120°C. Also, the photochromic properties of synthesized compounds were investigated in AcOH as a solvent under laboratory conditions at a temperature of 120°C. Moreover, the antibacterial and antioxidant activity of the synthesized compounds was investigated...

The cell membrane protein, dystroglycan, plays a crucial role in connecting the cytoskeleton of a variety of mammalian cells to the extracellular matrix. The α-subunit of dystroglycan (αDG) is characterized by a high level of glycosylation, including a unique O-mannosyl matriglycan. This specific glycosylation is essential for binding of αDG to extracellular matrix ligands effectively. A subset of muscular dystrophies, called dystroglycanopathies, are associated with aberrant, dysfunctional glycosylation of αDG...

This density functional theory (DFT) study explores the efficacy of cooperative catalytic systems in enabling the ionic hydrogenation of N2 with H2 , leading to NH3 formation. A set of N-heterocyclic carbene-based pincer tungsten/molybdenum metal complexes of the form [(PCP)M1 (H)2 ] (M1 = W/Mo) were chosen to bind N2 at the respective metal centres. Simultaneously, cationic rhodium/iridium complexes of type [Cp*M2 {2-(2-pyridyl)phenyl}(CH3 CN)]+ (Cp* = C5 (CH3 )5 and M2 = Rh/Ir), are employed as cooperative coordination partners for heterolytic H2 splitting...

Chemokine receptors are relevant targets for a multitude of immunological diseases, but drug attrition for these receptors is remarkably high. While many drug discovery programs have been pursued, most prospective drugs failed in the follow-up studies due to clinical inefficacy, and hence there is a clear need for alternative approaches. Allosteric modulators of receptor function represent an excellent opportunity for novel drugs, as they modulate receptor activation in a controlled manner and display increased selectivity, and their pharmacological profile can be insurmountable...

Curcuminoids and their complexes continue to attract attention in medicinal chemistry, but little attention has been given to their metabolic derivatives. Here, the first examples of (arene)Ru(II) complexes with curcuminoid metabolites, tetrahydrocurcumin (THcurcH), and tetrahydrobisdesmethoxycurcumin (THbdcurcH) were prepared and characterized. The neutral complexes [Ru(arene)(THcurc)Cl] and [Ru(arene)(THbdcurc)Cl] (arene = cymene, benzene, or hexamethylbenzene) were characterized by NMR spectroscopy and ESI mass spectrometry, and the crystal structures of the three complexes were determined by X-ray diffraction analysis...

Atomically precise nanoclusters hold promise for supramolecular assembly and (opto)electronic- as well as magnetic materials. Herein, this work reports that treating palladium(0) precursors with a triphosphirane affords strongly colored Pd8 (PDip)6 that is fully characterized by mass spectrometry, heteronuclear and Cross-Polarization Magic-Angle Spinning (CP-MAS) NMR-, infrared (IR), UV-vis, and X-ray photoelectron (XP) spectroscopies, single-crystal X-Ray diffraction (sc-XRD), mass spectrometry, and cyclovoltammetry (CV)...

Recent development of amyloid-β (Aβ)-targeted immunotherapies for Alzheimer's disease (AD) have highlighted the need for accurate diagnostic methods. Antibody-based positron emission tomography (PET) ligands are well suited for this purpose as they can be directed toward the same target as the therapeutic antibody. Bispecific, brain-penetrating antibodies can achieve sufficient brain concentrations, but their slow blood clearance remains a challenge, since it prolongs the time required to achieve a target-specific PET signal...

The development of polyoxometalate chemistry not only is derived from the continuous discovery of novel polyoxometalates (POMs) but also stems from the exploitation of their new functionalities. In this work, we obtained a rigid sulfur-containing heterocyclic ligand-linking aggregate [N(CH3 )4 ]10 Na6 H6 [Ce8 (H2 O)26 W8 (HTDA)2 (TDA)2 O20 ][SeW4 O18 ]2 [SeW9 O33 ]4 ·112H2 O ( 1 ) (H2 TDA = 2,5-thiophenedicarboxylic acid). Its polyanionic unit consists of one [Ce4 (H2 O)13 W4 O10 (HTDA)(TDA)O10 ]18+ cluster and two kinds of Keggin-type [SeW4 O18 ] and [SeW9 O33 ] segments...

There is a growing need for efficient bioanalysis of oligonucleotide therapeutics. This broad class of molecules presents numerous challenges relative to traditional small molecule therapeutics. Methodologies including ligand-binding assays or polymerase chain reaction may be fit-for-purpose in many instances, but liquid chromatography coupled to mass spectrometry (LC-MS) often delivers the best balance of sensitivity and selectivity. Over the last decade, we have engaged with many such molecules and derived insights into challenges and solutions...

The role of tannins (TA), a well-known abundant and ecologically friendly chelating ligand, in metal capture has long been studied. Different kinds of TA-containing adsorbents are synthesized for uranium capture, while most adsorbents suffer from unfavorable adsorption kinetics. Herein, the design and preparation of a TA-containing 2D crosslinked network adsorbent (TANP) is reported. The ≈1.8-nanometer-thick TANP films curl up into micrometer-scale pores, which contribute to fast mass transfer and full exposure of active sites...

Surface display technologies have been primarily developed for heterotrophic microbes, leaving photosynthetic counterparts like cyanobacteria with limited molecular tools. Here, we expanded upon surface display systems in Synechococcus elongatus PCC 7942 by modifying two outer-membrane proteins, SomA and Intimin, to display tags ( e.g. , SpyTag) to mediate physical interactions of living cyanobacteria with other biotic and abiotic targets. While re-engineered SomA constructs successfully translocated to the cell surface and could bind to compatible ligands, the efficacy of the best-performing designs was limited by a poorly-understood heterogeneity in the accessibility of the tags in living cells, resulting in low attachment penetrance...

The neuropeptide Y (NPY) Y4 receptor (Y4 R), a member of the family of NPY receptors, is physiologically activated by the linear 36-amino acid peptide pancreatic polypeptide (PP). The Y4 R is involved in the regulation of various biological processes, most importantly pancreatic secretion, gastrointestinal motility, and regulation of food intake. So far, Y4 R binding affinities have been mostly studied in radiochemical binding assays. Except for a few fluorescently labeled PP derivatives, fluorescence-tagged Y4 R ligands with high affinity have not been reported...

B cell transcriptomic signatures hold promise for the early prediction of vaccine-induced humoral immunity and vaccine protective efficacy. We performed a longitudinal study in 232 healthy adult participants before/after a 3rd dose of MMR (MMR3) vaccine. We assessed baseline and early transcriptional patterns in purified B cells and their association with measles-specific humoral immunity after MMR vaccination using two analytical methods ("per gene" linear models and joint analysis). Our study identified distinct early transcriptional signatures/genes following MMR3 that were associated with measles-specific neutralizing antibody titer and/or binding antibody titer...

The dendritic cell tetrameric lectin, DC-SIGN, and its closely related endothelial cell lectin, DC-SIGNR (collectively abbreviated as DC-SIGN/R) play a key role in the binding and transmission of deadly viruses, including Ebola, HIV, HCV, and SARS-CoV-2. Their virus binding/release processes involve a gradually acidifying environment following the natural intracellular trafficking pathways. Therefore, understanding DC-SIGN/R's pH-dependent binding properties with glycan ligands is of great importance. We have recently developed densely glycosylated gold nanoparticles (glycan-GNPs) as a powerful new tool for probing DC-SIGN/R multivalent lectin-glycan interaction (MLGI) mechanisms...

Halogen bonding is increasingly utilized in efforts to achieve high affinity and selectivity of molecules designed to bind proteins, making it paramount to understand the relationship between structure, dynamics, and thermodynamic driving forces. We present a detailed analysis addressing this problem using a series of protein-ligand complexes involving single halogen substitutions - F, Cl, Br, and I - and nearly identical structures. Isothermal titration calorimetry reveals an increasingly favorable binding enthalpy from F to I that correlates with the halogen size and σ-hole electropositive character, but is partially counteracted by unfavorable entropy, which is constant from F to Cl and Br, but worse for I...

This article presents the development of a distance-based thread analytical device (dTAD) integrated with an ion-imprinted polymer (IIP) for quantitative monitoring of zinc ions (Zn2+ ) in human urine samples. The IIP was easily chemically modified onto the thread channel using dithizone (DTZ) as a ligand to bind to Zn2+ with methacrylic acid (MAA) as a functional monomer and ethylene glycol dimethacrylate (EGDMA) as well as 2,2-azobisisobutyronitrile (AIBN) as cross-linking agents to enhance the selectivity for Zn2+ detection...

Cobalt-nitrogen-carbon (Co-N-C) catalysts with a CoN4 structure exhibit great potential for oxygen reduction reaction (ORR), but the imperfect adsorption energy toward oxygen species greatly limits their reduction efficiency and practical application potential. Here, F-coordinated Co-N-C catalysts with square-pyramidal CoN4 -F1 configuration are successfully synthesized using F atoms to regulate the axial coordination of Co centers via hydrothermal and chemical vapor deposition methods. During the synthesis process, the geometry structure of the Co atom converts from six-coordinated Co-F6 to square-pyramidal CoN4 -F1 in the coordinatively unsaturated state, which provides an open binding site for the O2 ...

Metal-organic frameworks (MOFs) are promising materials for gas sensing but are often limited to single-use detection. We demonstrate a hybridization strategy synergistically deploying conductive MOFs (cMOFs) and conductive polymers (cPs) as two complementary mixed ionic-electronic conductors in high-performing stand-alone chemiresistors. Our work presents significant improvement in i) sensor recovery kinetics, ii) cycling stability, and iii) dynamic range at room temperature. We demonstrate the effect of hybridization across well-studied cMOFs based on 2,3,6,7,10,11-hexahydroxytriphenylene (HHTP) and 2,3,6,7,10,11-hexaiminotripphenylene (HITP) ligands with varied metal nodes (Co, Cu, Ni)...

Metabotropic glutamate receptors belong to a family of G protein-coupled receptors that are obligate dimers and possess a large extracellular ligand-binding domain that is linked via a cysteine-rich domain to their 7-transmembrane domain1 . Upon activation, these receptors undergo a large conformational change to transmit the ligand binding signal from the extracellular ligand-binding domain to the G protein-coupling 7-transmembrane domain2 . In this manuscript, we propose a model for a sequential, multistep activation mechanism of metabotropic glutamate receptor subtype 5...