234,762 results match your criteria vitro binding

A distinct structure of Cas1-Cas2 complex provides insights into the mechanism for the longer spacer acquisition in Pyrococcus furiosus.

Int J Biol Macromol 2021 Apr 14. Epub 2021 Apr 14.

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu 610041, PR China. Electronic address:

In the adaptation stage of CRISPR-Cas systems, the Cas1-Cas2 integrase captures and integrates new invader-derived spacers into the CRISPR locus, serving as a molecular memory of prior infection. As of yet, the structural information of Cas1-Cas2 complex is available only for two species. Here we present the crystal structure of Cas1-Cas2 complex of Pyrococcus furiosus, which showed a distinct architecture from the known Cas1-Cas2 complexes. Read More

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Anti-inflammatory effects of FS48, the first potassium channel inhibitor from the salivary glands of the flea Xenopsylla cheopis.

J Biol Chem 2021 Apr 14:100670. Epub 2021 Apr 14.

Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China. Electronic address:

The voltage-gated potassium (Kv) 1.3 channel plays a crucial role in the immune responsiveness of T-lymphocytes and macrophages, presenting a potential target for treatment of immune- and inflammation related-diseases. FS48, a protein from the rodent flea Xenopsylla cheopis, shares the three disulfide bond feature of scorpion toxins. Read More

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SAGA and SAGA-like SLIK transcriptional coactivators are structurally and biochemically equivalent.

J Biol Chem 2021 Apr 14:100671. Epub 2021 Apr 14.

Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia. Electronic address:

The SAGA-like complex SLIK is a modified version of the Spt-Ada-Gcn5-Acetyltransferase (SAGA) complex. SLIK is formed through C-terminal truncation of the Spt7 SAGA subunit, causing loss of Spt8, one of the subunits that interacts with the TATA-binding protein (TBP). SLIK and SAGA are both coactivators of RNA polymerase II transcription in yeast and both SAGA and SLIK perform chromatin modifications. Read More

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Neuronal androgen receptor is required for activity dependent enhancement of peripheral nerve regeneration.

Dev Neurobiol 2021 Apr 17. Epub 2021 Apr 17.

Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia, USA.

Neuronal activity after nerve injury can enhance axon regeneration and the restoration of function. The mechanism for this enhancement relies in part on hormone receptors, and we previously demonstrated that systemic androgen receptor antagonism blocked the effect of exercise or electrical stimulation on enhancing axon regeneration after nerve injury in both sexes. Here, we tested the hypothesis that the site of this androgen receptor signaling is both neuronal and involves the classical, genomic signaling pathway. Read More

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Design, synthesis and biological evaluation of N-substituted indole-thiazolidinedione hybrid analogues as potential pancreatic lipase inhibitors.

Chem Biol Drug Des 2021 Apr 16. Epub 2021 Apr 16.

Laboratory of Natural Product Chemistry, Department of Pharmacy, Birla Institute of Technology and Science, Pilani (BITS Pilani), Pilani Campus, Pilani - 333 031, Rajasthan, India.

Pancreatic Lipase (PL) is a key enzyme responsible for 50-70% of dietary triglycerides, hence its inhibition is considered as a viable approach for the management of obesity. A series of indole-TZD hybrid analogues were synthesised, characterised, and evaluated for their PL inhibitory activity. Knoevenagel condensation of various substituted indole-3-carboxaldehyde with substituted thiazolidinediones resulted in the formation of titled analogues. Read More

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A cell based assay for evaluating binding and uptake of an antibody using hepatic nonparenchymal cells.

Sci Rep 2021 Apr 16;11(1):8383. Epub 2021 Apr 16.

Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Chiba, 260-0856, Japan.

Evaluation of the binding and uptake of an antibody in liver non-parenchymal cells (NPC), including liver sinusoidal endothelial cells, is important for revealing its pharmacokinetic (PK) behavior, since NPC has important roles in eliminating an antibody from the blood via the Fc fragment of IgG receptor IIB (FcγRIIB). However, there is currently no in vitro quantitative assay using NPC. This study reports on the development of a cell-based assay for evaluating the binding and uptake of such an antibody using liver NPC of mice and monkeys. Read More

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uPAR antibody (huATN-658) and Zometa reduce breast cancer growth and skeletal lesions.

Bone Res 2020 Apr 17;8(1):18. Epub 2020 Apr 17.

Department of Medicine, McGill University, Montréal, QC, H4A3J1, Canada.

Urokinase plasminogen activator receptor (uPAR) is implicated in tumor growth and metastasis due to its ability to activate latent growth factors, proteases, and different oncogenic signaling pathways upon binding to different ligands. Elevated uPAR expression is correlated with the increased aggressiveness of cancer cells, which led to its credentialing as an attractive diagnostic and therapeutic target in advanced solid cancer. Here, we examine the antitumor effects of a humanized anti-uPAR antibody (huATN-658) alone and in combination with the approved bisphosphonate Zometa (Zoledronic acid) on skeletal lesion through a series of studies in vitro and in vivo. Read More

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The SARS-CoV-2 Spike variant D614G favors an open conformational state.

Sci Adv 2021 Apr 16;7(16). Epub 2021 Apr 16.

Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.

The COVID-19 (coronavirus disease 2019) pandemic underwent a rapid transition with the emergence of a dominant viral variant (from the "D-form" to the "G-form") that carried an amino acid substitution D614G in its "Spike" protein. The G-form is more infectious in vitro and is associated with increased viral loads in the upper airways. To gain insight into the molecular-level underpinnings of these characteristics, we used microsecond all-atom simulations. Read More

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CD52/GPI- T-Cells Are Enriched for Alloreactive Specificity and Predict Acute Graft-Versus-Host-Disease After Stem Cell Transplantation.

Transplant Cell Ther 2021 Feb 25. Epub 2021 Feb 25.

Institute of Immunology and Immunotherapy, College of Medical and Dental Studies, University of Birmingham and Birmingham Health Partners, Birmingham, United Kingdom; Centre for Clinical Haematology, Queen Elizabeth NHS Foundation Trust and Birmingham Health Partners, Birmingham, United Kingdom.

Alemtuzumab is a CD52-specific lympho-depleting antibody. CD52- T cells emerge under alemtuzumab selection pressure. We sought to investigate the phenotype and function of the CD52- T cell fraction and related their presence to clinical outcome. Read More

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February 2021

Novel inhibitors of the main protease enzyme of SARS-CoV-2 identified via molecular dynamics simulation-guided in vitro assay.

Bioorg Chem 2021 Mar 29;111:104862. Epub 2021 Mar 29.

Institute of Biological Information Processing: Structural Biochemistry (IBI-7), Forschungszentrum Jülich, 52428 Jülich, Germany; Institute of Theoretical and Computational Chemistry, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany. Electronic address:

For the COVID-19 pandemic caused by SARS-CoV-2, there are currently no effective drugs or vaccines to treat this coronavirus infection. In this study, we focus on the main protease enzyme of SARS-CoV-2, 3CL, which is critical for viral replication. We employ explicit solvent molecular dynamics simulations of about 150 compounds docked into 3CL's binding site and that had emerged as good main protease ligands from our previous in silico screening of over 1. Read More

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S100B/RAGE/Ceramide signaling pathway is involved in sepsis-associated encephalopathy.

Life Sci 2021 Apr 13;277:119490. Epub 2021 Apr 13.

Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China. Electronic address:

Aims: Sepsis-associated encephalopathy (SAE) is one of the most common complications of sepsis, and it might lead to long-term cognitive dysfunction and disability. This study aimed to explore the role of S100 calcium binding protein B (S100B)/RAGE/ceramide signaling pathway in SAE.

Main Methods: FPS-ZM1 (an inhibitor of RAGE), myriocin and GW4869 (an inhibitor of ceramide) were used to explore the role of S100B/RAGE/ceramide in acute brain injury and long-term cognitive impairment in sepsis. Read More

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Piperlongumine inhibits the progression of osteosarcoma by downregulating the SOCS3/JAK2/STAT3 pathway via miR-30d-5p.

Life Sci 2021 Apr 15;277:119501. Epub 2021 Apr 15.

Department of Spine Surgery, People's Hospital of Longhua, Affiliated Hospital of Southern Medical University, Guangdong 518000, Shenzhen, China. Electronic address:

Aims: The present study evaluated the functions of Piperlongumine (PL) in osteosarcoma (OS) cell growth and metastasis both in vitro and in vivo.

Main Methods: MTT assay was conducted to test the cytotoxic effects of PL on the human osteoblasts line HFOB1.19 and the human normal chondrocyte line C28/I2T. Read More

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An α-synuclein decoy peptide prevents cytotoxic α-synuclein aggregation caused by fatty acid binding protein 3.

J Biol Chem 2021 Apr 13:100663. Epub 2021 Apr 13.

Department of Chemistry and Biotechnology, Faculty of Engineering/Graduate School of Engineering,; Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science,; Center for Research on Green Sustainable Chemistry, Tottori University, Tottori 680-8552, Japan. Electronic address:

α-synuclein (αSyn) is a protein known to form intracellular aggregates during the manifestation of Parkinson's disease. Previously, it was shown that αSyn aggregation was strongly suppressed in the midbrain region of mice that did not possess the gene encoding the lipid transport protein fatty acid binding protein 3 (FABP3). An interaction between these two proteins was detected in vitro, suggesting that FABP3 may play a role in the aggregation and deposition of αSyn in neurons. Read More

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Steady-state kinetic analysis of halogenase-supporting flavin reductases BorF and AbeF reveals different kinetic mechanisms.

Arch Biochem Biophys 2021 Apr 13:108874. Epub 2021 Apr 13.

Department of Chemistry and Biochemistry, College of Natural Sciences and Mathematics, The University of Toledo Toledo, OH, 43606, USA. Electronic address:

The short-chain flavin reductases BorF and AbeF reduce FAD to FADH, which is then used by flavin-dependent halogenases (BorH and AbeH respectively) to regioselectively chlorinate tryptophan in the biosynthesis of indolotryptoline natural products. Recombinant AbeF and BorF were overexpressed and purified as homodimers from E. coli, and copurified with substoichiometric amounts of FAD, which could be easily removed. Read More

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Anthelmintic activity of a nanoformulation based on thiophenes identified in Tagetes patula L. (Asteraceae) against the small ruminant nematode Haemonchus contortus.

Acta Trop 2021 Apr 13:105920. Epub 2021 Apr 13.

Chemistry Institute, São Paulo State University (UNESP), Araraquara (SP), Brazil.

The synthesis of thiophenic compounds, previously identified in Tagetes patula, revealed that 4-(5'-(hydroxymethyl)-[2,2'-bithiophene]-5-yl)but-3-yn-1-ol), or simply Thio1, has a pronounced in vitro anthelmintic effect against Haemonchus contortus, showing 100% efficacy in the egg hatch and larval development tests presenting EC = 0.1731 mg.mL and EC = 0. Read More

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Region- and receptor-specific effects of chronic social stress on the central serotonergic system in mice.

IBRO Neurosci Rep 2021 Jun 3;10:8-16. Epub 2021 Feb 3.

Department of Life Sciences, University of Roehampton, London SW15 4JD, UK.

Serotonin (5-HT), via its receptors expressed in discrete brain regions, modulates aversion and reward processing and is implicated in various psychiatric disorders including depression. Stressful experiences affect central serotonergic activity and act as a risk factor for depression; this can be modelled preclinically. In adult male C57BL/6J mice, 15-day chronic social stress (CSS) leads to depression-relevant behavioural states, including increased aversion and reduced reward sensitivity. Read More

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Myeloperoxidase Targets Apolipoprotein A-I for Site-Specific Tyrosine Chlorination in Atherosclerotic Lesions and Generates Dysfunctional High-Density Lipoprotein.

Chem Res Toxicol 2021 Apr 16. Epub 2021 Apr 16.

Key Laboratory of Functional Small Organic Molecule, Ministry of Education; Jiangxi Key Laboratory of Green Chemistry, College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang 330022, China.

We previously demonstrated that apolipoprotein A-I (apoA-I), the major protein component of high-density lipoprotein (HDL), is an important target for myeloperoxidase (MPO)-catalyzed tyrosine chlorination in the circulation of subjects with cardiovascular diseases. Oxidation of apoA-I by MPO has been reported to deprive HDL of its protective properties. However, the potential effects of MPO-mediated site-specific tyrosine chlorination of apoA-I on dysfunctional HDL formation and atherosclerosis was unclear. Read More

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Identification and functional characterization of a new flavonoid synthase gene MdFLS1 from apple.

Planta 2021 Apr 15;253(5):105. Epub 2021 Apr 15.

School of Pharmacy, Liaocheng University, Liaocheng, Shandong, 250000, People's Republic of China.

Main Conclusion: The flavonoid synthase gene MdFLS1 from apple, which possibly plays an important role in anthocyanin synthesis, accumulates in the purple-red branches of Malus 'Pink spire'. Flavonoid metabolism serves an important function in plant growth and development. In this study, we selected 20 varieties of apple lines, 10 green and ten red branches, from the plant nursery of Qingdao Agriculture Academy. Read More

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Target-Driven Design of a Coumarinyl Chalcone Scaffold Based Novel EF2 Kinase Inhibitor Suppresses Breast Cancer Growth .

ACS Pharmacol Transl Sci 2021 Apr 30;4(2):926-940. Epub 2021 Mar 30.

Department of Experimental Therapeutics, The University of Texas, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 422, Houston, Texas 77030, United States.

Eukaryotic elongation factor 2 kinase (eEF-2K) is an unusual alpha kinase involved in protein synthesis through phosphorylation of elongation factor 2 (EF2). eEF-2K is highly overexpressed in breast cancer, and its activity is associated with significantly shortened patient survival and proven to be a potential molecular target in breast cancer. The crystal structure of eEF-2K remains unknown, and there is no potent, safe, and effective inhibitor available for clinical applications. Read More

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Macrocyclic Gq Protein Inhibitors FR900359 and/or YM-254890-Fit for Translation?

ACS Pharmacol Transl Sci 2021 Apr 19;4(2):888-897. Epub 2021 Feb 19.

PharmaCenter Bonn, Pharmaceutical Institute, Pharmaceutical & Medicinal Chemistry, University of Bonn, An der Immenburg 4, 53121 Bonn, Germany.

Guanine nucleotide-binding proteins (G proteins) transduce extracellular signals received by G protein-coupled receptors (GPCRs) to intracellular signaling cascades. While GPCRs represent the largest class of drug targets, G protein inhibition has only recently been recognized as a novel strategy for treating complex diseases such as asthma, inflammation, and cancer. The structurally similar macrocyclic depsipeptides FR900359 (FR) and YM-254890 (YM) are potent selective inhibitors of the Gq subfamily of G proteins. Read More

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Exploring the Cytotoxic Effects of the Extracts and Bioactive Triterpenoids from against Oral Squamous Cell Carcinoma: A Scientific Interpretation and Validation of Indigenous Knowledge.

ACS Pharmacol Transl Sci 2021 Apr 9;4(2):834-847. Epub 2021 Mar 9.

Chemical Sciences and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology (CSIR-NIIST), Thiruvananthapuram 695019, India.

Triterpenoids are ubiquitously distributed secondary metabolites, primarily scrutinized as a source of medication and preventive measures for various chronic diseases. The ease of isolation and excellent pharmacological properties of triterpenoids are notable reasons behind the exponential rise of extensive research on the bioactive triterpenoids over the past few decades. Herein, we attempted to explore the anticancer potential of the fruit extract of the ethnomedicinal plant against oral squamous cell carcinoma (OSCC) and have exclusively attributed the efficacy of the extracts to the presence of two triterpenoids, namely, betulinic acid (BA) and koetjapic acid (KA). Read More

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Tropane-Based Ibogaine Analog Rescues Folding-Deficient Serotonin and Dopamine Transporters.

ACS Pharmacol Transl Sci 2021 Apr 28;4(2):503-516. Epub 2020 Aug 28.

Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse, Intramural Research Program, Baltimore, Maryland 21224, United States.

Missense mutations that give rise to protein misfolding are rare, but collectively, defective protein folding diseases are consequential. Folding deficiencies are amenable to pharmacological correction (pharmacochaperoning), but the underlying mechanisms remain enigmatic. Ibogaine and its active metabolite noribogaine correct folding defects in the dopamine transporter (DAT), but they rescue only a very limited number of folding-deficient DAT mutant proteins, which give rise to infantile Parkinsonism and dystonia. Read More

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Transcriptional Enhancer Factor Domain Family member 4 Exerts an Oncogenic Role in Hepatocellular Carcinoma by Hippo-Independent Regulation of Heat Shock Protein 70 Family Members.

Hepatol Commun 2021 Apr 20;5(4):661-674. Epub 2021 Jan 20.

Institute of Medical Genetics and Pathology University Hospital Basel Basel Switzerland.

Transcriptional enhancer factor domain family member 4 (TEAD4) is a downstream effector of the conserved Hippo signaling pathway, regulating the expression of genes involved in cell proliferation and differentiation. It is up-regulated in several cancer types and is associated with metastasis and poor prognosis. However, its role in hepatocellular carcinoma (HCC) remains largely unexplored. Read More

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Photobiomodulation Therapy Ameliorates Glutamatergic Dysfunction in Mice with Chronic Unpredictable Mild Stress-Induced Depression.

Oxid Med Cell Longev 2021 29;2021:6678276. Epub 2021 Mar 29.

MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China.

Accumulating evidence indicates that dysfunction of the glutamatergic neurotransmission has been widely involved in the pathophysiology and treatment of depression. Photobiomodulation therapy (PBMT) has been demonstrated to regulate neuronal function both and . Herein, we aim to investigate whether the antidepressant phenotype of PBMT is associated with the improvement of glutamatergic dysfunction and to explore the mechanisms involved. Read More

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Targeting long noncoding RNA PMIF facilitates osteoprogenitor cells migrating to bone formation surface to promote bone formation during aging.

Theranostics 2021 20;11(11):5585-5604. Epub 2021 Mar 20.

Lab for Bone Metabolism, Xi'an Key Laboratory of Special Medicine and Health Engineering, Key Lab for Space Biosciences and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, China.

The migration of mesenchymal osteoprogenitor cells (OPCs) to bone formation surface is the initial step of osteoblastogenesis before they undergo osteoblast differentiation and maturation for governing bone formation. However, whether the migration capacity of OPCs is compromised during aging and how it contributes to the aging-related bone formation reduction remain unexplored. In the present study, we identified a migration inhibitory factor (, long noncoding RNA PMIF) and examined whether targeting lnc-PMIF could facilitate osteoprogenitor cells migrating to bone formation surface to promote bone formation during aging. Read More

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Homogeneous tumor targeting with a single dose of HER2-targeted albumin-binding domain-fused nanobody-drug conjugates results in long-lasting tumor remission in mice.

Theranostics 2021 13;11(11):5525-5538. Epub 2021 Mar 13.

Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, Utrecht, The Netherlands.

The non-homogenous distribution of antibody-drug conjugates (ADCs) within solid tumors is a major limiting factor for their wide clinical application. Nanobodies have been shown to rapidly penetrate into xenografts, achieving more homogeneous tumor targeting. However, their rapid renal clearance can hamper their application as nanobody drug conjugates (NDCs). Read More

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STAT3 ameliorates cognitive deficits via regulation of NMDAR expression in an Alzheimer's disease animal model.

Theranostics 2021 13;11(11):5511-5524. Epub 2021 Mar 13.

Department of Pathophysiology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Key Laboratory of Ministry of Education of China and Hubei Province for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Abnormal tau accumulation in the brain has a positively correlation with neurodegeneration and memory deterioration, but the mechanism underlying tau-associated synaptic and cognitive impairments remains unclear. Our previous work has found that human full length tau (hTau) accumulation activated signal transducer and activator of transcription-1 (STAT1) to suppress N-methyl-D-aspartate receptors (NMDARs) expression, followed by memory deficits. STAT3 also belongs to STAT protein family and is reported to involve in regulation of synaptic plasticity and cognition. Read More

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Hsa_circ_0030042 regulates abnormal autophagy and protects atherosclerotic plaque stability by targeting eIF4A3.

Theranostics 2021 12;11(11):5404-5417. Epub 2021 Mar 12.

The Key Laboratory of Cardiovascular Remodelling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, 250012 Jinan, China.

Abnormal autophagic death of endothelial cells is detrimental to plaque structure as endothelial loss promotes lesional thrombosis. As emerging functional biomarkers, circular RNAs (circRNAs) are involved in various diseases, including cardiovascular. This study is aimed to determine the role of hsa_circ_0030042 in abnormal endothelial cell autophagy and plaque stability. Read More

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Characterization and Mechanism of Linearized-Microcystinase Involved in Bacterial Degradation of Microcystins.

Front Microbiol 2021 30;12:646084. Epub 2021 Mar 30.

Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University, Changsha, China.

Microcystins (MCs) are extremely hazardous to the ecological environment and public health. How to control and remove MCs is an unsolved problem all over the world. Some microbes and their enzymes are thought to be effective in degrading MCs. Read More

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Para-chloro-2-[F]fluoroethyl-etomidate: A promising new PET radiotracer for adrenocortical imaging.

Int J Med Sci 2021 21;18(10):2187-2196. Epub 2021 Mar 21.

Medicinal Chemistry and Uppsala University.

[C]Metomidate ([C]MTO), the methyl ester analogue of etomidate, was developed as a positron emission tomography (PET) radiotracer for adrenocortical tumours and has also been suggested for imaging in primary aldosteronism (PA). A disadvantage of [C]MTO is the rather high non-specific binding in the liver, which impacts both visualization and quantification of the uptake in the right adrenal gland. Furthermore, the short 20-minute half-life of carbon-11 is a logistic challenge in the clinical setting. Read More

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