Activation of the TCR Complex by Small Chemical Compounds

2013 ◽  
pp. 25-39 ◽  
Author(s):  
Christine Louis-Dit-Sully ◽  
Wolfgang W. A. Schamel
Keyword(s):  
Chemical Compounds ◽  
Small Chemical

scholarly journals MMHub, a database for the mulberry metabolome

Database ◽  
2020 ◽  
Vol 2020 ◽  
Author(s):  
Dong Li ◽  
Bi Ma ◽  
Xiaofei Xu ◽  
Guo Chen ◽  
Tian Li ◽  
...  
Keyword(s):  
Mass Spectra ◽  
Chemical Compounds ◽  
Bioactive Metabolites ◽  
Molecular Formula ◽  
Experimental Conditions ◽  
Chemical Structures ◽  
Pubchem Compound ◽  
Specific Distribution ◽  
Small Chemical ◽  
Metabolome Data

Abstract Mulberry is an important economic crop plant and traditional medicine. It contains a huge array of bioactive metabolites such as flavonoids, amino acids, alkaloids and vitamins. Consequently, mulberry has received increasing attention in recent years. MMHub (version 1.0) is the first open public repository of mass spectra of small chemical compounds (<1000 Da) in mulberry leaves. The database contains 936 electrospray ionization tandem mass spectrometry (ESI-MS2) data and lists the specific distribution of compounds in 91 mulberry resources with two biological duplicates. ESI-MS2 data were obtained under non-standardized and independent experimental conditions. In total, 124 metabolites were identified or tentatively annotated and details of 90 metabolites with associated chemical structures have been deposited in the database. Supporting information such as PubChem compound information, molecular formula and metabolite classification are also provided in the MS2 spectral tag library. The MMHub provides important and comprehensive metabolome data for scientists working with mulberry. This information will be useful for the screening of quality resources and specific metabolites of mulberry. Database URL: https://biodb.swu.edu.cn/mmdb/

scholarly journals A review on drug repurposing applicable to COVID-19

2020 ◽  
Author(s):  
Serena Dotolo ◽  
Anna Marabotti ◽  
Angelo Facchiano ◽  
Roberto Tagliaferri
Keyword(s):  
Artificial Intelligence ◽  
Drug Target ◽  
Lower Cost ◽  
Drug Repositioning ◽  
Drug Repurposing ◽  
Chemical Compounds ◽  
The Moment ◽  
New Applications ◽  
Novel Drug ◽  
Small Chemical

Abstract Drug repurposing involves the identification of new applications for existing drugs at a lower cost and in a shorter time. There are different computational drug-repurposing strategies and some of these approaches have been applied to the coronavirus disease 2019 (COVID-19) pandemic. Computational drug-repositioning approaches applied to COVID-19 can be broadly categorized into (i) network-based models, (ii) structure-based approaches and (iii) artificial intelligence (AI) approaches. Network-based approaches are divided into two categories: network-based clustering approaches and network-based propagation approaches. Both of them allowed to annotate some important patterns, to identify proteins that are functionally associated with COVID-19 and to discover novel drug–disease or drug–target relationships useful for new therapies. Structure-based approaches allowed to identify small chemical compounds able to bind macromolecular targets to evaluate how a chemical compound can interact with the biological counterpart, trying to find new applications for existing drugs. AI-based networks appear, at the moment, less relevant since they need more data for their application.

An ON1–OFF–ON2 electrochemiluminescence response: combining the intermolecular specific binding with a radical scavenger

2015 ◽  
Vol 51 (56) ◽  
pp. 11236-11239 ◽  
Author(s):  
Xiaojiao Du ◽  
Ding Jiang ◽  
Nan Hao ◽  
Qian Liu ◽  
Jing Qian ◽  
...  
Keyword(s):  
Chemical Reactions ◽  
Specific Binding ◽  
Chemical Compounds ◽  
Sensitive Detection ◽  
Radical Scavenger ◽  
Organophosphate Pesticides ◽  
Highly Sensitive ◽  
Highly Sensitive Detection ◽  
Small Chemical

The electrochemiluminescence (ECL) technique was combined with the “ON1–OFF–ON2” strategy based on the chemical reactions and specific binding among different small chemical compounds for the highly sensitive detection of nonelectroactive organophosphate pesticides.

scholarly journals A screening pipeline identifies a broad-spectrum inhibitor of bacterial AB toxins with cross protection against influenza A virus H1N1 and SARS-CoV-2

2021 ◽  
Author(s):  
Yu Wu ◽  
Nassim Mahtal ◽  
Lea Swistak ◽  
Sara Sagadiev ◽  
Mridu Acharya ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
High Throughput Screening ◽  
Influenza A ◽  
Influenza Infection ◽  
Chemical Compounds ◽  
B Subunit ◽  
Early Endosomes ◽  
Cytotoxic Necrotizing Factor 1 ◽  
Small Chemical

A challenge for the development of host-targeted anti-infectives against a large spectrum of AB-like toxin-producing bacteria encompasses the identification of chemical compounds corrupting toxin transport through both endolysosomal and retrograde pathways. Here, we performed a high-throughput screening of small chemical compounds blocking active Rac1 proteasomal degradation triggered by the Cytotoxic Necrotizing Factor-1 (CNF1) toxin, followed by orthogonal screens against two AB toxins hijacking defined endolysosomal (Diphtheria toxin) or retrograde (Shiga-like toxin 1) pathways to intoxicate cells. This led to the identification of the molecule N-(3,3-diphenylpropyl)-1-propyl-4-piperidinamine, referred to as C910. This compound induces the swelling of EEA1-positive early endosomes, in absence of PIKfyve kinase inhibition, and disturbs the trafficking of CNF1 and the B-subunit of Shiga toxin along the endolysosomal or retrograde pathways, respectively. Together, we show that C910 protects cells against 8 bacterial AB toxins including large clostridial glucosylating toxins from Clostridium difficile. Of interest, C910 also reduced viral infection in vitro including influenza A virus subtype H1N1 and SARS-CoV-2. Moreover, parenteral administration of C910 to the mice resulted in its accumulation in lung tissues and reduced lethal influenza infection.

Promising Biologic Agents and Small Chemical Compounds

2009 ◽  
pp. 372-378 ◽  
Author(s):  
Christopher G. Meyer ◽  
E. William St. Clair
Keyword(s):  
Chemical Compounds ◽  
Biologic Agents ◽  
Small Chemical

scholarly journals Generating CHARMM compatible force field parameters for atrazine

2016 ◽  
Vol 3 (1) ◽  
pp. 1-8
Author(s):  
János Ecker
Keyword(s):  
Molecular Dynamics ◽  
Md Simulation ◽  
Bond Angle ◽  
Chemical Compounds ◽  
And Topology ◽  
Herbicide Atrazine ◽  
Synthetic Drug ◽  
Force Field Parameters ◽  
Dynamics Simulations ◽  
Small Chemical

There are many synthetic, drug-like molecules whose interactions with large biomolecules could be partly described by molecular dynamics studies. The parameters necessary to perform an MD simulation are available for biomolecules (proteins, nucleic acids, lipids, carbohydrates) and for many other small chemical compounds with biological relevance. In case of uncharacterized molecules, parameter sets can be calculated using quantummechanical calculations. The optimized geometry, van der Waals, charge, bond, angle and torsion parameters for the photosystem II-inhibitor herbicide, atrazine, were calculated and integrated into a CHARMM-compatible parameter file. The file (.par) is available, along with the coordinates (.pdb), structure (.psf) and topology (.top), and with this four type of data, atrazine may be part of CHARMM-based molecular dynamics simulations, therefore, its interactions with biomolecules can be studied.

scholarly journals Identification and Characterization of a Novel Family of Selective Antifungal Compounds (CANBEFs) That Interfere with Fungal Protein Synthesis

2015 ◽  
Vol 59 (9) ◽  
pp. 5631-5640 ◽  
Author(s):  
Gabriel Mircus ◽  
Nathaniel Albert ◽  
Dafna Ben-Yaakov ◽  
Dodo Chikvashvili ◽  
Yona Shadkchan ◽  
...  
Keyword(s):  
Cell Wall ◽  
Protein Synthesis ◽  
Aspergillus Nidulans ◽  
Galleria Mellonella ◽  
Fungal Infections ◽  
Chemical Compounds ◽  
Fungal Cell ◽  
Content Type ◽  
Mammalian Cell Lines ◽  
Small Chemical

ABSTRACTInvasive mycotic infections have become more common during recent decades, posing an increasing threat to public health. However, despite the growing needs, treatments for invasive fungal infections remain unsatisfactory and are limited to a small number of antifungals. The aim of this study was to identify novel fungal cell wall inhibitors from a library of small chemical compounds using a conditional protein kinase C (PKC)-expressing strain ofAspergillus nidulanssensitive to cell wall-active agents. Eight “hit” compounds affecting cell wall integrity were identified from a screen of 35,000 small chemical compounds. Five shared a common basic molecular structure of 4-chloro-6-arylamino-7-nitro-benzofurazane (CANBEF). The most potent compound, CANBEF-24, was characterized further and was shown to inhibit the growth of pathogenicAspergillus,Candida,Fusarium, andRhizopusisolates at micromolar concentrations but not to affect the growth of mammalian cell lines. CANBEF-24 demonstrated strong synergy in combination with caspofungin, an antifungal that inhibits cell wall biosynthesis. Genetic and biochemical analyses withAspergillus nidulansandSaccharomyces cerevisiaeindicated that CANBEFs selectively inhibit fungal rRNA maturation and protein synthesis, suggesting that their effect on the cell wall is indirect. CANBEFs were nontoxic in insect (Galleria mellonella,Drosophila melanogaster) and mouse models of fungal infection. Preliminary evidence showing no therapeutic benefit in these models suggests that further cycles of optimization are needed for the development of this novel class of compounds for systemic use.

scholarly journals Direct conversion of human fibroblasts to brown adipocytes by small chemical compounds

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Yukimasa Takeda ◽  
Yoshinori Harada ◽  
Toshikazu Yoshikawa ◽  
Ping Dai
Keyword(s):  
Human Fibroblasts ◽  
Chemical Compounds ◽  
Direct Conversion ◽  
Brown Adipocytes ◽  
Small Chemical

scholarly journals Protein Aggregation Inhibitors as Disease-Modifying Therapies for Polyglutamine Diseases

2021 ◽  
Vol 15 ◽  
Author(s):  
Eiko N. Minakawa ◽  
Yoshitaka Nagai
Keyword(s):  
Gene Silencing ◽  
Chemical Compounds ◽  
Causative Role ◽  
Disease Modifying Therapies ◽  
Recent Advances ◽  
Aggregation Inhibitors ◽  
Disease Modifying ◽  
Polyq Diseases ◽  
Small Chemical ◽  
Β Sheet

The polyglutamine (polyQ) diseases are a group of inherited neurodegenerative diseases caused by the abnormal expansion of a CAG trinucleotide repeat that are translated into an expanded polyQ stretch in the disease-causative proteins. The expanded polyQ stretch itself plays a critical disease-causative role in the pathomechanisms underlying polyQ diseases. Notably, the expanded polyQ stretch undergoes a conformational transition from the native monomer into the β-sheet-rich monomer, followed by the formation of soluble oligomers and then insoluble aggregates with amyloid fibrillar structures. The intermediate soluble species including the β-sheet-rich monomer and oligomers exhibit substantial neurotoxicity. Therefore, protein conformation stabilization and aggregation inhibition that target the upstream of the insoluble aggregate formation would be a promising approach toward the development of disease-modifying therapies for polyQ diseases. PolyQ aggregation inhibitors of different chemical categories, such as intrabodies, peptides, and small chemical compounds, have been identified through intensive screening methods. Among them, recent advances in the brain delivery methods of several peptides and the screening of small chemical compounds have brought them closer to clinical utility. Notably, the recent discovery of arginine as a potent conformation stabilizer and aggregation inhibitor of polyQ proteins both in vitro and in vivo have paved way to the clinical trial for the patients with polyQ diseases. Meanwhile, expression reduction of expanded polyQ proteins per se would be another promising approach toward disease modification of polyQ diseases. Gene silencing, especially by antisense oligonucleotides (ASOs), have succeeded in reducing the expression of polyQ proteins in the animal models of various polyQ diseases by targeting the aberrant mRNA with expanded CAG repeats. Of note, some of these ASOs have recently been translated into clinical trials. Here we overview and discuss these recent advances toward the development of disease modifying therapies for polyQ diseases. We envision that combination therapies using aggregation inhibitors and gene silencing would meet the needs of the patients with polyQ diseases and their caregivers in the near future to delay or prevent the onset and progression of these currently intractable diseases.

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