Browse
Submit Data
Databases
API
Help

Dataset Information

9 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Target protein-oriented isolation of Hes1 dimer inhibitors using protein based methods.

ABSTRACT: Natural products isolation using protein based methods is an attractive for obtaining bioactive compounds. To discover neural stem cell (NSC) differentiation activators, we isolated eight inhibitors of Hes1 dimer formation from Psidium guajava using the Hes1-Hes1 interaction fluorescent plate assay and one inhibitor from Terminalia chebula using the Hes1-immobilized beads method. Of the isolated compounds, gallic acid (8) and 4-O-(4"-O-galloyl-?-L-rhamnopyranosyl)ellagic acid (11) showed potent Hes1 dimer formation inhibitory activity, with IC50 values of 10.3 and 2.53 ?M, respectively. Compound 11 accelerated the differentiation activity of C17.2 NSC cells dose dependently, increasing the number of neurons with a 125% increase (5 ?M) compared to the control.

SUBMITTER: Arai MA

PROVIDER: S-EPMC6987128 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Target protein-oriented isolation of Hes1 dimer inhibitors using protein based methods.

Arai Midori A MA Morita Kaori K Kawano Haruka H Makita Yuna Y Hashimoto Manami M Suganami Akiko A Tamura Yutaka Y Sadhu Samir K SK Ahmed Firoj F Ishibashi Masami M

Scientific reports 20200128 1

Natural products isolation using protein based methods is an attractive for obtaining bioactive compounds. To discover neural stem cell (NSC) differentiation activators, we isolated eight inhibitors of Hes1 dimer formation from Psidium guajava using the Hes1-Hes1 interaction fluorescent plate assay and one inhibitor from Terminalia chebula using the Hes1-immobilized beads method. Of the isolated compounds, gallic acid (8) and 4-O-(4"-O-galloyl-α-L-rhamnopyranosyl)ellagic acid (11) showed potent ...[more]

PMID: 31992824

Similar Datasets

Hes1 inhibitor isolated by target protein oriented natural products isolation (TPO-NAPI) of differentiation activators of neural stem cells.

Project description:The Hes1 dimer inhibitor, agalloside (2), which can accelerate the differentiation of neural stem cells is described. Six natural products, including one new natural product, which bind to Hes1 were rapidly isolated by a developed "target protein oriented natural products isolation" (TPO-NAPI) method using Hes1-immobilized beads. Of the six compounds, 2 inhibited Hes1 dimer formation at both the protein- and cellular level. Neural stem cells treated with 2 differentiated to neurons with longer neurites than cells treated with varproic acid or retinoic acid. Moreover, 2 exhibited specificity for neurons. This promotion of differentiation was supported by an increase in the mRNA expression of the proneural genes, Mash1 and Ngn2, which were inhibited by Hes1.

| S-EPMC5963671 | biostudies-literature

Scrutinizing GW-Based Methods Using the Hubbard Dimer.

Project description:Using the simple (symmetric) Hubbard dimer, we analyze some important features of the GW approximation. We show that the problem of the existence of multiple quasiparticle solutions in the (perturbative) one-shot GW method and its partially self-consistent version is solved by full self-consistency. We also analyze the neutral excitation spectrum using the Bethe-Salpeter equation (BSE) formalism within the standard GW approximation and find, in particular, that 1) some neutral excitation energies become complex when the electron-electron interaction U increases, which can be traced back to the approximate nature of the GW quasiparticle energies; 2) the BSE formalism yields accurate correlation energies over a wide range of U when the trace (or plasmon) formula is employed; 3) the trace formula is sensitive to the occurrence of complex excitation energies (especially singlet), while the expression obtained from the adiabatic-connection fluctuation-dissipation theorem (ACFDT) is more stable (yet less accurate); 4) the trace formula has the correct behavior for weak (i.e., small U) interaction, unlike the ACFDT expression.

| S-EPMC8586429 | biostudies-literature

Structure-oriented methods for protein NMR data analysis.

Project description: Not available

| S-EPMC2944251 | biostudies-literature

Discovery of WD Repeat-Containing Protein 5 (WDR5)-MYC Inhibitors Using Fragment-Based Methods and Structure-Based Design.

Project description:The frequent deregulation of MYC and its elevated expression via multiple mechanisms drives cells to a tumorigenic state. Indeed, MYC is overexpressed in up to ∼50% of human cancers and is considered a highly validated anticancer target. Recently, we discovered that WD repeat-containing protein 5 (WDR5) binds to MYC and is a critical cofactor required for the recruitment of MYC to its target genes and reported the first small molecule inhibitors of the WDR5-MYC interaction using structure-based design. These compounds display high binding affinity, but have poor physicochemical properties and are hence not suitable for in vivo studies. Herein, we conducted an NMR-based fragment screening to identify additional chemical matter and, using a structure-based approach, we merged a fragment hit with the previously reported sulfonamide series. Compounds in this series can disrupt the WDR5-MYC interaction in cells, and as a consequence, we observed a reduction of MYC localization to chromatin.

| S-EPMC7187413 | biostudies-literature

Comparative Analysis of Mass-Spectrometry-Based Proteomic Methods for Protein Target Discovery Using a One-Pot Approach.

Project description:Recently, several mass-spectrometry- and protein-denaturation-based proteomic methods have been developed to facilitate protein target discovery efforts in drug mode-of-action studies. These methods, which include the stability of proteins from rates of oxidation (SPROX), pulse proteolysis (PP), chemical denaturation and protein precipitation (CPP), and thermal proteome profiling (TPP) techniques, have been used in an increasing number of applications in recent years. However, while the advantages and disadvantages to using these different techniques have been reviewed, the analytical characteristics of these methods have not been directly compared. Reported here is such a direct comparison using the well-studied immunosuppressive drug, cyclosporine A (CsA), and the proteins in a yeast cell lysate. Also described is a one-pot strategy that can be utilized with each technique to streamline data acquisition and analysis. We find that there are benefits to utilizing all four strategies for protein target discovery including increased proteomic coverage and reduced false positive rates that approach 0%. Moreover, the one-pot strategy described here makes such an experiment feasible, because of the 10-fold reduction in reagent costs and instrument time it affords.

| S-EPMC7441748 | biostudies-literature

Benchmark study of different chromatin isolation methods using the E2Fa transcription factor

Project description:Genome-wide identification of transcription factor (TF) binding sites is pivotal to our understanding of gene expression regulation. Although much progress has been made in the determination of potential binding regions of proteins by chromatin immunoprecipitation (ChIP), this method has some inherent limitations regarding DNA enrichment efficiency and antibody necessity. Here, we report an alternative strategy for assaying in vivo TF-DNA binding in Arabidopsis thaliana cells by tandem chromatin affinity purification (TChAP). Evaluation of TChAP using the E2Fa TF and comparison with traditional ChIP and single chromatin affinity purification illustrates the suitability of TChAP and provides a resource for exploring the E2Fa transcriptional network. Integration with transcriptome, cis-regulatory element, functional enrichment, and co-expression network analyses demonstrates the quality of the E2Fa TChAP-seq data and validates the identification of new direct E2Fa targets. TChAP enhances both TF target mapping throughput, by circumventing issues related to antibody availability, and output, by improving DNA enrichment efficiency.

2014-02-04 | GSE53422 | GEO

RNA Isolation Methods - Diverse Biofluids

Project description:To evaluate performance of different extra cellular RNA isolation methods in biofluids

2023-09-30 | GSE242613 | GEO

Benchmark study of different chromatin isolation methods using the E2Fa transcription factor

2014-02-04 | E-GEOD-53422 | biostudies-arrayexpress

Identification of Enzyme Inhibitors Using Therapeutic Target Protein - Magnetic Nanoparticle Conjugates.

Project description:Target protein - magnetic nanoparticle (MNP) conjugates, i.e. ?-glucosidase-MNP and protein tyrosine phosphatase 1B (PTP1B)-MNP, were prepared and evaluated for the first time for affinity extraction of the enzyme inhibitors from herbal extracts. Four ligands extracted from granati pericarpium were identified by ESI-MS analysis. In vitro tests indicated that they inhibited both ?-glucosidase and PTP1B, two important target proteins for diabetic treatment.

| S-EPMC3378064 | biostudies-literature

DNA target sequence identification mechanism for dimer-active protein complexes.

Project description:Sequence-specific DNA-binding proteins must quickly and reliably localize specific target sites on DNA. This search process has been well characterized for monomeric proteins, but it remains poorly understood for systems that require assembly into dimers or oligomers at the target site. We present a single-molecule study of the target-search mechanism of protelomerase TelK, a recombinase-like protein that is only active as a dimer. We show that TelK undergoes 1D diffusion on non-target DNA as a monomer, and it immobilizes upon dimerization even in the absence of a DNA target site. We further show that dimeric TelK condenses non-target DNA, forming a tightly bound nucleoprotein complex. Together with theoretical calculations and molecular dynamics simulations, we present a novel target-search model for TelK, which may be generalizable to other dimer and oligomer-active proteins.

| S-EPMC3575837 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data