155,301 results match your criteria high affinity

Distinct glycolytic pathway regulation in liver, tumour and skeletal muscle of mice with cancer cachexia.

Cell Biochem Funct 2021 Jun 15. Epub 2021 Jun 15.

Department of Exercise Science and Health Promotion, Florida Atlantic University, Boca Raton, Florida, USA.

Energetically inefficient inter-organ substrate shuttles are proposed contributors to cachexia-related weight loss. Here, we examined glycolytic pathway metabolites, enzyme activity and transport proteins in skeletal muscle, liver and tumours of mice with cachexia-related weight loss induced by colon-26 cancer cells. Skeletal muscle of cachexic mice had increased [L-lactate]/[pyruvate], LDH activity and lactate transporter MCT1. Read More

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Na,K-ATPase α4, and Not Na,K-ATPase α1, is the Main Contributor to Sperm Motility, But its High Ouabain Binding Affinity Site is Not Required for Male Fertility in Mice.

J Membr Biol 2021 Jun 15. Epub 2021 Jun 15.

Department of Molecular and Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas, KS, 66160, USA.

Mammalian sperm express two Na,K-ATPase (NKA) isoforms, Na,K-ATPase α4 (NKAα4) and Na,K-ATPase α1 (NKAα1). While NKAα4 is critical to sperm motility, the role of NKAα1 in sperm movement remains unknown. We determined this here using a genetic and pharmacological approach, modifying the affinity of NKAα1 and NKAα4 for the inhibitor ouabain to selectively block the function of each isoform. Read More

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Design, synthesis, and biological evaluation of novel benzimidazole derivatives as sphingosine kinase 1 inhibitor.

Arch Pharm (Weinheim) 2021 Jun 15:e2100080. Epub 2021 Jun 15.

Department of Chemistry of Natural and Microbial Products, Division of Pharmaceutical and Drug Industries Research, National Research Centre, Cairo, Egypt.

Sphingosine kinase 1 (SphK1) has emerged as an attractive drug target for different diseases. Recently, discovered SphK1 inhibitors have been recommended in cancer therapeutics; however, selectivity and potency are great challenges. In this study, a novel series of benzimidazoles was synthesized and evaluated as SphK1 inhibitors. Read More

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Deconvoluting the T Cell Response to SARS-CoV-2: Specificity Versus Chance and Cognate Cross-Reactivity.

Front Immunol 2021 28;12:635942. Epub 2021 May 28.

Research and Development, Cellular Technology Ltd., Shaker Heights, OH, United States.

SARS-CoV-2 infection takes a mild or clinically inapparent course in the majority of humans who contract this virus. After such individuals have cleared the virus, only the detection of SARS-CoV-2-specific immunological memory can reveal the exposure, and hopefully the establishment of immune protection. With most viral infections, the presence of specific serum antibodies has provided a reliable biomarker for the exposure to the virus of interest. Read More

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Reconstituting T cell receptor selection in-silico.

Genes Immun 2021 Jun 14. Epub 2021 Jun 14.

Department of Population and Data Sciences, UT Southwestern Medical Center, Dallas, TX, USA.

Each T cell receptor (TCR) gene is created without regard for which substances (antigens) the receptor can recognize. T cell selection culls developing T cells when their TCRs (i) fail to recognize major histocompatibility complexes (MHCs) that act as antigen presenting platforms or (ii) recognize with high affinity self-antigens derived from healthy cells and tissue. While T cell selection has been thoroughly studied, little is known about which TCRs are retained or removed by this process. Read More

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Analysis of bacterial flora of indigo fermentation fluids utilizing composted indigo leaves (sukumo) and indigo extracted from plants (Ryukyu-ai and Indian indigo).

J Biosci Bioeng 2021 Jun 11. Epub 2021 Jun 11.

Bioproduction Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukisamu-Higashi, Toyohira-ku, Sapporo 062-8517, Japan; Laboratory of Environmental Microbiology, Graduate School of Agriculture, Hokkaido University, Kita-ku, Sapporo 060-8589, Japan. Electronic address:

Indigo is a fabric dye that requires reduction by microbial activity or chemical reagents to render it soluble in water. Sources of indigo for fermentation are primarily divided into composted indigo-containing plants and indigo extracted from plants. To elucidate the factors responsible for bacterial diversity, and for sustaining reduced state of indigo in different preparations, this study assessed fermentation-derived fluids using composted plant leaves, sukumo, and extracted indigo (Ryukyu-ai paste, and Indian indigo cake) prepared using different procedures. Read More

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Landscape and selection of vaccine epitopes in SARS-CoV-2.

Genome Med 2021 06 14;13(1):101. Epub 2021 Jun 14.

Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, CB# 7295, Chapel Hill, NC, 27599-7295, USA.

Background: Early in the pandemic, we designed a SARS-CoV-2 peptide vaccine containing epitope regions optimized for concurrent B cell, CD4 T cell, and CD8 T cell stimulation. The rationale for this design was to drive both humoral and cellular immunity with high specificity while avoiding undesired effects such as antibody-dependent enhancement (ADE).

Methods: We explored the set of computationally predicted SARS-CoV-2 HLA-I and HLA-II ligands, examining protein source, concurrent human/murine coverage, and population coverage. Read More

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Assigning confidence to molecular property prediction.

Expert Opin Drug Discov 2021 Jun 15:1-15. Epub 2021 Jun 15.

Chemical Physics Theory Group, Department of Chemistry, University of Toronto, Toronto, Canada.

: Computational modeling has rapidly advanced over the last decades. Recently, machine learning has emerged as a powerful and cost-effective strategy to learn from existing datasets and perform predictions on unseen molecules. Accordingly, the explosive rise of data-driven techniques raises an important question: What confidence can be assigned to molecular property predictions and what techniques can be used?: The authors discuss popular strategies for predicting molecular properties, their corresponding uncertainty sources and methods to quantify uncertainty. Read More

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Biomimetic nanochannels for the discrimination of sialylated glycans a tug-of-war between glycan binding and polymer shrinkage.

Chem Sci 2019 Dec 3;11(3):748-756. Epub 2019 Dec 3.

Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences 457 Zhongshan Road Dalian 116023 China

Sialylated glycans that are attached to cell surface mediate diverse cellular processes such as immune responses, pathogen binding, and cancer progression. Precise determination of sialylated glycans, particularly their linkage isomers that can trigger distinct biological events and are indicative of different cancer types, remains a challenge, due to their complicated composition and limited structural differences. Here, we present a biomimetic nanochannels system integrated with the responsive polymer polyethyleneimine--glucopyranoside (Glc-PEI) to solve this problem. Read More

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December 2019

Precipitation-free high-affinity multivalent binding by inline lectin ligands.

Chem Sci 2020 Apr 27;11(20):5227-5237. Epub 2020 Apr 27.

University of Konstanz, Department of Chemistry, Konstanz Research School Chemical Biology (KoRS-CB) Universitätsstraße 10 78457 Konstanz Germany

Multivalent ligand-protein interactions are a key concept in biology mediating, for example, signalling and adhesion. Multivalent ligands often have tremendously increased binding affinities. However, they also can cause crosslinking of receptor molecules leading to precipitation of ligand-receptor complexes. Read More

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A fluorescent molecular imaging probe with selectivity for soluble tau aggregated protein.

Chem Sci 2020 Apr 21;11(18):4773-4778. Epub 2020 Apr 21.

Molecular Imaging Chemistry Laboratory, Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge Cambridge UK

Soluble forms of aggregated tau misfolded protein, generally termed oligomers, are considered to be the most toxic species of the different assembly states that are the pathological components of neurodegenerative disorders. Therefore, a critical biomedical need exists for imaging probes that can identify and quantify them. We have designed and synthesized a novel fluorescent probe, for which binding and selectivity profiles towards aggregated tau and Aβ proteins were assessed. Read More

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A highly stable RNA aptamer probe for the retinoblastoma protein in live cells.

Chem Sci 2020 Apr 21;11(17):4467-4474. Epub 2020 Apr 21.

Department of Chemistry, Imperial College London 80 Wood Lane W12 0BZ UK

Although RNA aptamers can show comparable or better specificity and affinity to antibodies and have the advantage of being able to access different live cell compartments, they are often much less stable . We report here the first aptamer that binds human retinoblastoma protein (RB) and is stable in live cells. RB is both a key protein in cell cycle control and also a tumour suppressor. Read More

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Synthesis, conformational analysis and assays of an anti-cancer vaccine that features an unnatural antigen based on an sp-iminosugar fragment.

Chem Sci 2020 Mar 27;11(15):3996-4006. Epub 2020 Mar 27.

Departamento de Química, Universidad de La Rioja, Centro de Investigación en Síntesis Química E-26006 Logroño Spain

The Tn antigen (GalNAc-α-1--Thr/Ser) is a well-known tumor-associated carbohydrate determinant. The use of glycopeptides that incorporate this structure has become a significant and promising niche of research owing to their potential use as anticancer vaccines. Herein, the conformational preferences of a glycopeptide with an unnatural Tn antigen, characterized by a threonine decorated with an sp-iminosugar-type α-GalNAc mimic, have been studied both in solution, by combining NMR spectroscopy and molecular dynamics simulations, and in the solid state bound to an anti-mucin-1 (MUC1) antibody, by X-ray crystallography. Read More

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Antibody-recruiting protein-catalyzed capture agents to combat antibiotic-resistant bacteria.

Chem Sci 2020 Feb 12;11(11):3054-3067. Epub 2020 Feb 12.

Institute for Systems Biology 401 Terry Ave North Seattle 98109 USA

Antibiotic resistant infections are projected to cause over 10 million deaths by 2050, yet the development of new antibiotics has slowed. This points to an urgent need for methodologies for the rapid development of antibiotics against emerging drug resistant pathogens. We report on a generalizable combined computational and synthetic approach, called antibody-recruiting protein-catalyzed capture agents (AR-PCCs), to address this challenge. Read More

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February 2020

An ornithine-rich dodecapeptide with improved proteolytic stability selectively kills gram-negative food-borne pathogens and its action mode on Escherichia coli O157:H7.

Int J Food Microbiol 2021 Jun 8;352:109281. Epub 2021 Jun 8.

State Key Laboratory of Chemical Biology and Drug Discovery and Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong.

Food-borne pathogenic bacteria are dispersed throughout the entire chain of the food industry. However, many food preservatives are limited by poor biocompatibility such as cumulative poisoning. The antimicrobial peptide is increasingly regarded as a promising preservative in food research due to its high bioactivity and low cytotoxicity. Read More

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Targeting immunodominant Bet v 1 epitopes with monoclonal antibodies prevents the birch allergic response.

J Allergy Clin Immunol 2021 Jun 11. Epub 2021 Jun 11.

Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA. Electronic address:

Background: Blocking the major cat allergen, Fel d 1, with monoclonal antibodies (mAbs) was effective in preventing an acute cat-allergic response.

Objective: We sought to extend the allergen-specific antibody approach and demonstrate that a combination of mAbs targeting Bet v 1, the immunodominant and most abundant allergenic protein in birch pollen, can prevent the birch-allergic response.

Methods: Bet v 1-specific mAbs, REGN5713, REGN5714 and REGN5715, were isolated using the VelocImmune platform. Read More

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Synthesis of magnetic nanoparticles functionalized with histidine and nickel to immobilize His-tagged enzymes using β-galactosidase as a model.

Int J Biol Macromol 2021 Jun 11. Epub 2021 Jun 11.

Food Biotechnology Laboratory, Biotechnology Graduate Program, University of Vale do Taquari - Univates, Lajeado, RS, Brazil. Electronic address:

The aim of this study was to synthesize iron magnetic nanoparticles functionalized with histidine and nickel (FeO-His-Ni) to be used as support materials for oriented immobilization of His-tagged recombinant enzymes of high molecular weight, using β-galactosidase as a model. The texture, morphology, magnetism, thermal stability, pH and temperature reaction conditions, and the kinetic parameters of the biocatalyst obtained were assessed. In addition, the operational stability of the biocatalyst in the lactose hydrolysis of cheese whey and skim milk by batch processes was also assessed. Read More

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The release inhibition of organic substances from microplastics in the presence of algal derived organic matters: Influence of the molecular weight-dependent inhibition heterogeneities.

Environ Res 2021 Jun 11:111424. Epub 2021 Jun 11.

School of Energy and Environment, Anhui University of Technology, Maanshan, 243002, China.

As the emerging contaminants, the behavior and fate of microplastics (MPs) were highly related to the interactions with surrounding organic matters. However, information on the effects of molecular sizes of organic matters on the interaction is still lacking. In this study, the bulk algal-derived organic matter (AOM) samples were obtained and further fractionated into high molecular weight (HMW-, 1kDa-0. Read More

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Association of circulating fibroblast growth factor-2 with progression of HIV-chronic kidney diseases in children.

Pediatr Nephrol 2021 Jun 14. Epub 2021 Jun 14.

Child Health Research Center, Department of Pediatrics, School of Medicine, University of Virginia, Room 2120, MR4 Building, 409 Lane Road, Charlottesville, VA, 22908, USA.

Background: Children living with HIV frequently show high plasma levels of fibroblast growth factor-2 (FGF-2/bFGF). FGF-2 accelerates the progression of several experimental kidney diseases; however, the role of circulating FGF-2 in childhood HIV-chronic kidney diseases (HIV-CKDs) is unknown. We carried out this study to determine whether high plasma FGF-2 levels were associated with the development of HIV-CKDs in children. Read More

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McpT, a broad range carboxylate chemoreceptor in .

J Bacteriol 2021 Jun 14:JB0021621. Epub 2021 Jun 14.

Department of Biological Sciences, Virginia Tech, Blacksburg, VA 24061, USA.

Chemoreceptors enable the legume symbiont to detect and respond to specific chemicals released from their host plant alfalfa, which allows the establishment of a nitrogen-fixing symbiosis. The periplasmic region (PR) of transmembrane chemoreceptors act as the sensory input module for chemotaxis systems via binding of specific ligands, either directly or indirectly. has six transmembrane and two cytosolic chemoreceptors. Read More

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An excimer to exciplex transition through realization of donor-acceptor interactions in luminescent solvent-free liquids.

Nanoscale 2021 Jun 14. Epub 2021 Jun 14.

Organic Chemistry Division, National Chemical Laboratory (CSIR-NCL), Dr. Homi Bhabha Road, Pune-411008, India. and Academy of Scientific and Innovative Research (AcSIR), Ghaziabad-201 002, India.

Luminescent solvent-free organic liquids are known for their enhanced quantum yield, color tunability, and availability of a matrix for other dopants to generate hybrid luminescent materials with improved features for newer applications. Herein, we report a donor-acceptor based luminescent "exciplex liquid" by utilizing the slightly different electron affinity of the acceptor molecules. A red-shifted broad exciplex emission exhibited by the donor-acceptor pair even at a lower concentration of the acceptor (0. Read More

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Doubly Stochastic Normalization of the Gaussian Kernel Is Robust to Heteroskedastic Noise.

SIAM J Math Data Sci 2021 23;3(1):388-413. Epub 2021 Mar 23.

Program in Applied Mathematics, Yale University.

A fundamental step in many data-analysis techniques is the construction of an affinity matrix describing similarities between data points. When the data points reside in Euclidean space, a widespread approach is to from an affinity matrix by the Gaussian kernel with pairwise distances, and to follow with a certain normalization (e.g. Read More

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FRET-Based Genetically Encoded Sensor to Monitor Silver Ions.

ACS Omega 2021 Jun 27;6(22):14164-14173. Epub 2021 May 27.

Department of Biosciences, Jamia Millia Islamia, New Delhi 110025, India.

Silver is commonly used in wound dressing, photography, health care products, laboratories, pharmacy, biomedical devices, and several industrial purposes. Silver (Ag) ions are more toxic pollutants widely scattered in the open environment by natural processes and dispersed in soil, air, and water bodies. Ag binds with metallothionein, macroglobulins, and albumins, which may lead to the alteration of various enzymatic metabolic pathways. Read More

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Stabilizing Triglyceride in Methanol Emulsions via a Magnetic Pickering Interfacial Catalyst for Efficient Transesterification under Static Conditions.

ACS Omega 2021 Jun 24;6(22):14138-14147. Epub 2021 May 24.

State Key Laboratory Breeding Base of Green Chemistry-Synthesis Technology, Zhejiang Province Key Laboratory of Biofuel, Biodiesel Laboratory of China Petroleum and Chemical Industry Federation, College of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310014, P. R. China.

Pickering emulsion systems provide potential platforms for simultaneously intensifying and catalyzing transesterification between triglyceride and methanol under static conditions. However, realizing static transesterification with high biodiesel yield is still challenging due to low emulsion stability at the reaction temperature. Here, a series of magnetically recyclable Pickering interfacial catalysts (PICs) with similar surface affinities but different densities were constructed as stabilizers of a soybean oil/methanol emulsion. Read More

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Female Adolescent Soccer Players Utilize Different Neuromuscular Strategies Between Limbs During the Propulsion Phase of a Lateral Vertical Jump.

Int J Sports Phys Ther 2021 Jun 2;16(3):695-703. Epub 2021 Jun 2.

Northwestern University.

Background: Multiplanar dynamic stability is an important unilateral function in soccer performance but has been scarcely examined in female soccer players. The lateral vertical jump task assesses unilateral functional performance, and energy generation contribution examines how each joint (hip, knee, ankle) contributes to the vertical component of the vertical jump phase to measure inter- and intra-limb differences.

Purpose: To examine dominant versus non-dominant limb performance using energy generation contribution of the hip, knee, and ankle during the vertical jump component of the lateral vertical jump. Read More

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Correlation between in vitro binding activity of sweeteners to cloned human sweet taste receptor and sensory evaluation.

Food Sci Biotechnol 2021 May 18;30(5):675-682. Epub 2021 May 18.

Department of Nutritional Science and Food Management, Ewha Womans University, Seoul, 03760 Republic of Korea.

The human sweet taste receptor is a TAS1R2/TAS1R3 heterodimer. To investigate the correlation between the in vitro affinity of sweeteners with stably expressed human sweet taste receptor in HEK-293 cells and human sensory evaluation, the receptor-ligand activity of bulk (sucrose, D-fructose, and allulose) and high-intensity sweeteners (saccharin, rebaudioside A, rebaudioside M, and neohesperidin dihydrochalcone) was compared by analyzing the Ca release. The relative potency of the sweeteners was identified over a wide concentration range for ECs. Read More

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Encoded, click-reactive DNA-binding domains for programmable capture of specific chromatin segments.

Chem Sci 2020 Oct 20;11(46):12506-12511. Epub 2020 Oct 20.

Faculty of Chemistry and Chemical Biology, TU Dortmund University Otto-Hahn Str. 4a 44227 Dortmund Germany.

Enrichment of chromatin segments from specific genomic loci of living cells is an important goal in chromatin biology, since it enables establishing local molecular compositions as the basis of locus function. A central enrichment strategy relies on the expression of DNA-binding domains that selectively interact with a local target sequence followed by fixation and isolation of the associated chromatin segment. The efficiency and selectivity of this approach critically depend on the employed enrichment tag and the strategy used for its introduction into the DNA-binding domain or close-by proteins. Read More

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October 2020

Unveiling the molecular mechanism of SARS-CoV-2 main protease inhibition from 137 crystal structures using algebraic topology and deep learning.

Chem Sci 2020 Sep 30;11(44):12036-12046. Epub 2020 Sep 30.

Department of Mathematics, Michigan State University MI 48824 USA

Currently, there is neither effective antiviral drugs nor vaccine for coronavirus disease 2019 (COVID-19) caused by acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Due to its high conservativeness and low similarity with human genes, SARS-CoV-2 main protease (M) is one of the most favorable drug targets. However, the current understanding of the molecular mechanism of M inhibition is limited by the lack of reliable binding affinity ranking and prediction of existing structures of M-inhibitor complexes. Read More

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September 2020

Carbohydrate-binding module -mannosylation alters binding selectivity to cellulose and lignin.

Chem Sci 2020 Aug 19;11(34):9262-9271. Epub 2020 Aug 19.

Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College Beijing 100050 China

Improved understanding of the effect of protein glycosylation is expected to provide the foundation for the design of protein glycoengineering strategies. In this study, we examine the impact of -glycosylation on the binding selectivity of a model Family 1 carbohydrate-binding module (CBM), which has been shown to be one of the primary sub-domains responsible for non-productive lignin binding in multi-modular cellulases. Specifically, we examine the relationship between glycan structure and the binding specificity of the CBM to cellulose and lignin substrates. Read More

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Elusive structural changes of New Delhi metallo-β-lactamase revealed by ultraviolet photodissociation mass spectrometry.

Chem Sci 2020 Aug 11;11(33):8999-9010. Epub 2020 Aug 11.

Department of Chemistry, University of Texas at Austin Austin TX 78712 USA

We use mass spectrometry (MS), under denaturing and non-denaturing solution conditions, along with ultraviolet photodissociation (UVPD) to characterize structural variations in New Delhi metallo-β-lactamase (NDM) upon perturbation by ligands or mutation. Mapping changes in the abundances and distributions of fragment ions enables sensitive detection of structural alterations throughout the protein. Binding of three covalent inhibitors was characterized: a pentafluorphenyl ester, an -aryloxycarbonyl hydroxamate, and ebselen. Read More

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