scholarly journals Differential Sensing of Saccharides Based on an Array of Fluorinated Benzosiloxaborole Receptors

Sensors ◽  
2020 ◽  
Vol 20 (12) ◽  
pp. 3540
Author(s):  
Paweł Ćwik ◽  
Patrycja Ciosek-Skibińska ◽  
Marcin Zabadaj ◽  
Sergiusz Luliński ◽  
Krzysztof Durka ◽  
...  
Keyword(s):  
Binding Sites ◽  
Clustering Analysis ◽  
Lewis Acidity ◽  
Alizarin Red ◽  
Molecular Receptors ◽  
Potential Binding ◽  
Receptor Array ◽  
Ph Conditions ◽  
Shed Light ◽  
Boron Center

Fluorinated benzosiloxaboroles–silicon congeners of benzoxaboroles, were synthesized and tested as molecular receptors for mono- and disaccharides. The receptors differed in the Lewis acidity of the boron center as well as in the number of potential binding sites. The calculated stability constants indicated different binding affinity of benzosiloxaborole derivatives towards selected saccharides, enabling their classification using a receptor array-based sensing. Unique fluorescence fingerprints were created on the basis of competitive interactions of the studied receptors with both Alizarin Red S (ARS) and tested saccharide molecules. Detailed chemometric analysis of the obtained fluorescence data (based on partial least squares-discriminant analysis and hierarchical clustering analysis) provided the differential sensing of common saccharides, in particular the differentiation between glucose and fructose. In addition, DFT calculations were carried out to shed light on the binding mechanism under different pH conditions.

scholarly journals EPEN-30. C11ORF95-RELA FUSION PROTEIN ENGAGES NOVEL GENOMIC LOCI TO DRIVE MURINE EPENDYMOMA GROWTH

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii314-iii314
Author(s):  
Amir Arabzade ◽  
Yanhua Zhao ◽  
Srinidhi Varadharajan ◽  
Hsiao-Chi Chen ◽  
Austin Stuckert ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Binding Sites ◽  
Molecular Targets ◽  
Lead Target ◽  
Open Chromatin ◽  
Rna Seq ◽  
In Utero Electroporation ◽  
Pathway Activation ◽  
Mouse Cells ◽  
Shed Light

Abstract RATIONALE Over 70% of supratentorial (ST) ependymoma are characterized by an oncogenic fusion between C11ORF95 and RELA. C11ORF95-RELA fusion is frequently the sole genetic driver detected in ST ependymoma, thus ranking this genomic event as a lead target for therapeutic investigation. RELA is a transcription factor (TF) central to mediating NF-kB pathway activation in processes such as inflammation, cellular metabolism, and chemotaxis. HYPOTHESIS: We posited that C11ORF95-RELA acts as an oncogenic TF that aberrantly shapes the tumor epigenome to drive aberrant transcription. Approach: To this end we developed an in utero electroporation (IUE) mouse model of ependymoma to express C11ORF95-RELA during embryonic development. Our IUE approach allowed us to develop C11ORF95-RELA driven tumor models and cell lines. We comprehensively characterized the epigenome and transcriptome of C11ORF95-RELA fusion driven mouse cells by H3K27ac ChIP-seq, ATAC-seq, and RNA-seq. RESULTS This data revealed that: 1) C11ORF95-RELA directly engages ‘open’ chromatin and is enriched at regions with known RELA TF binding sites as well as novel genomic loci/motifs, 2) C11ORF95-RELA preferentially binds to both H3K27ac (active) enhancers and promoters, and 3) Bound C11ORF95-RELA promoter loci are associated with increased transcription of genes shared with human ependymoma. CONCLUSION Our findings shed light on the transcriptional mechanisms of C11ORF95-RELA, and reveal downstream targets that may represent cancer dependency genes and molecular targets.

scholarly journals Connecting Structure with Kinetics of Single-Stranded DNA Fluctuations that Provide Potential Binding Sites for Replication Proteins

2021 ◽  
Vol 120 (3) ◽  
pp. 219a
Author(s):  
Claire Albrecht ◽  
Brett A. Israels ◽  
Chloe Chvatal ◽  
Peter H. von Hippel ◽  
Andrew H. Marcus
Keyword(s):  
Binding Sites ◽  
Replication Proteins ◽  
Single Stranded Dna ◽  
Potential Binding ◽  
Kinetics Of

scholarly journals Spectroscopic BIL-SFG Invariance Hides the Chaotropic Effect of Protons at the Air-Water Interface

Atmosphere ◽  
2018 ◽  
Vol 9 (10) ◽  
pp. 396 ◽  
Author(s):  
Simone Pezzotti ◽  
Marie-Pierre Gaigeot
Keyword(s):  
Water Structure ◽  
Md Simulations ◽  
Interfacial Structure ◽  
Water Interface ◽  
Sum Frequency ◽  
Hydronium Ion ◽  
Sum Frequency Generation Spectroscopy ◽  
Air Water Interface ◽  
Ph Conditions ◽  
Shed Light

The knowledge of the water structure at the interface with the air in acidic pH conditions is of utmost importance for chemistry in the atmosphere. We shed light on the acidic air-water (AW) interfacial structure by DFT-MD simulations of the interface containing one hydronium ion coupled with theoretical SFG (Sum Frequency Generation) spectroscopy. The interpretation of SFG spectra at charged interfaces requires a deconvolution of the signal into BIL (Binding Interfacial Layer) and DL (Diffuse Layer) SFG contributions, which is achieved here, and hence reveals that even though H 3 O + has a chaotropic effect on the BIL water structure (by weakening the 2D-HBond-Network observed at the neat air-water interface) it has no direct probing in SFG spectroscopy. The changes observed experimentally in the SFG of the acidic AW interface from the SFG at the neat AW are shown here to be solely due to the DL-SFG contribution to the spectroscopy. Such BIL-SFG and DL-SFG deconvolution rationalizes the experimental SFG data in the literature, while the hydronium chaotropic effect on the water 2D-HBond-Network in the BIL can be put in perspective of the decrease in surface tension at acidic AW interfaces.

scholarly journals An In-Silico Study of Stable and Environment-Friendly Oryza sativa Urease

2020 ◽  
Vol 11 (3) ◽  
pp. 10238-10247
Keyword(s):  
Oryza Sativa ◽  
Binding Sites ◽  
3D Structure ◽  
Crop Productivity ◽  
Environment Friendly ◽  
Potential Binding ◽  
Urease Enzyme ◽  
In Silico Study ◽  
Stable Mutant ◽  
Detrimental Impact

Urea is one of the most extensively used fertilizers in agriculture but has a detrimental impact on the environment. One of the strategies to reduce this impact can be engineering modified plants containing urease enzyme with a considerably higher affinity for urea so that the urea applied in the fields can be significantly reduced. In this study, we have selected Oryza sativa Urease and generated stable mutants having a high affinity for urea. We modeled the 3D structure of the enzyme and identified the potential binding sites by analyzing the binding sites of similar proteins, i.e., 48 urea binding proteins. We found that mutation of Arg578 with Cys near the substrate-binding site of Oryza sativa Urease leads to a stable mutant protein that has a higher binding affinity for urea. This study will lead to a generation of environment-friendly, stable, genetically modified rice crop that consumes lesser urea, without compromising with crop productivity.

scholarly journals INSILICO STUDIES OF OXIME PRODRUG OF GLICLAZIDE AGAINST SULPHONYLUREA RECEPTORS (SUR 1)

2017 ◽  
Vol 9 (4) ◽  
pp. 100
Author(s):  
Surendran Vijayaraj ◽  
Kannekanti Chaithanya Veena
Keyword(s):  
Binding Sites ◽  
Pancreatic Beta Cells ◽  
Molecular Targets ◽  
Docking Studies ◽  
Docking Analysis ◽  
Potential Binding ◽  
In Silico Study ◽  
Molecular Docking Analysis ◽  
Autodock 4.2

Objective: Objective of the study is to perform a molecular docking analysis of novel oxime prodrug of gliclazide against SUR1 receptor.Methods: Sulfonylurea receptors (SUR) are membrane proteins which are the molecular targets of the sulfonylurea class of anti-diabetic drugs whose mechanism of action is to promote insulin release from pancreatic beta cells. Oxime prodrug of gliclazide a better soluble derivative of gliclazide is used for enhancement of bioavailability of gliclazide. Autodock 4.2 software was used for docking studies. Ligand 2D structures were drawn using ChemDraw Ultra 7.0. Binding sites, docking poses and interactions of the ligand with SUR1 receptors were studied by pymol software.Results: The docking studies suggest that potential binding sites of oxime prodrug of gliclazide exhibiting all the major interactions such as hydrogen bonding, hydrophobic interaction and electrostatic interaction with GLU43, LEU11, LEU 40, ILE17 GLU 68, GLN72 residues of SUR1. The binding energy of complexes are also found to be minimal forming stable complexes.Conclusion: In silico study of oxime prodrug of gliclazide conforms, the binding of oxime prodrug of glicalzide with SUR1 receptors which effectively controls the release insulin to regulate plasma glucose concentrations. Hence, the oxime prodrug of gliclazide could be a potent anti-diabetic target molecule which may be worth for further in vitro and in vivostudies. 

Phosphate‐Rich Biomimetic Peptides Shed Light on High‐Affinity Hyperphosphorylated Uranyl Binding Sites in Phosphoproteins

2019 ◽  
Vol 25 (36) ◽  
pp. 8570-8578 ◽  
Author(s):  
Fanny A. Laporte ◽  
Colette Lebrun ◽  
Claude Vidaud ◽  
Pascale Delangle
Keyword(s):  
Binding Sites ◽  
High Affinity ◽  
Shed Light

scholarly journals The Retinoid and Non-Retinoid Ligands of the Rod Visual G Protein-Coupled Receptor

2019 ◽  
Vol 20 (24) ◽  
pp. 6218 ◽  
Author(s):  
Joseph T. Ortega ◽  
Beata Jastrzebska
Keyword(s):  
Drug Discovery ◽  
G Protein ◽  
Binding Sites ◽  
Binding Pocket ◽  
Biologically Active ◽  
Surface Receptors ◽  
Beneficial Effects ◽  
Light Sensing ◽  
Potential Binding ◽  
G Protein Coupled

G protein-coupled receptors (GPCRs) play a predominant role in the drug discovery effort. These cell surface receptors are activated by a variety of specific ligands that bind to the orthosteric binding pocket located in the extracellular part of the receptor. In addition, the potential binding sites located on the surface of the receptor enable their allosteric modulation with critical consequences for their function and pharmacology. For decades, drug discovery focused on targeting the GPCR orthosteric binding sites. However, finding that GPCRs can be modulated allosterically opened a new venue for developing novel pharmacological modulators with higher specificity. Alternatively, focus on discovering of non-retinoid small molecules beneficial in retinopathies associated with mutations in rhodopsin is currently a fast-growing pharmacological field. In this review, we summarize the accumulated knowledge on retinoid ligands and non-retinoid modulators of the light-sensing GPCR, rhodopsin and their potential in combating the specific vision-related pathologies. Also, recent findings reporting the potential of biologically active compounds derived from natural products as potent rod opsin modulators with beneficial effects against degenerative diseases related to this receptor are highlighted here.

scholarly journals Unique reactivity of B in B[Ge9Y3]3 (Y = H, CH3, BO, CN): formation of a Lewis base

2019 ◽  
Vol 21 (42) ◽  
pp. 23301-23304
Author(s):  
G. Naaresh Reddy ◽  
Rakesh Parida ◽  
R. Inostroza-Rivera ◽  
Arindam Chakraborty ◽  
Puru Jena ◽  
...  
Keyword(s):  
Lewis Acid ◽  
Lewis Base ◽  
Lewis Acidity ◽  
Boron Compounds ◽  
Zintl Ion ◽  
Acid Nature ◽  
Boron Center

Boron compounds usually exhibit Lewis acidity at the boron center due to the presence of vacant p-orbitals. But using Zintl-ion based groups (Ge9Y3, Y = H, CH3, BO, CN), we can alter Lewis acid nature of B to a Lewis base.

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