Browse
Submit Data
Databases
API
Help

Dataset Information

6 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Trypsin-Instructed Self-Assembly on Endoplasmic Reticulum for Selectively Inhibiting Cancer Cells: Dedicated to Professor George M. Whitesides on the occasion of his 80th birthday.

ABSTRACT: Selectively targeting the endoplasmic reticulum (ER) of cancer cells, though promising a new strategy for cancer therapy, remains underdeveloped. Enzyme-instructed self-assembly (EISA) is emerging as a promising approach for selectively targeting ER of cancer cells. This work reports an easily accessible branched peptide that consists of a D-tetrapeptide backbone and a branch with the sequence of KYDKKKKDG (K: lysine; Y: tyrosine; D: aspratic acid; G: glycine), being an EISA substrate of typsin-1 (PRSS1), selectively inhibits cancer cells. Depending on the type of cells, the level of PRSS1 expression dictates the cytotoxicity of the branched peptide. Moreover, immunostaining and fluorescent imaging reveal that PRSS1 overexpresses on the ER of a high-grade serous ovarian cancer cell line (OVSAHO). The overexpression of PRSS1 renders the branched peptide to exhibit high selectivity against OVSAHO by the in situ formation of the peptide assemblies on the ER of OVSAHO cells, which causes ER stress and eventual cell death. This work, illustrating trypsin-guided EISA for inhibiting cancer cells by enzymatic reaction on ER for the first time, offers a new way to target the subcellular organelles of cancer cells for potential cancer therapy.

SUBMITTER: Kim BJ

PROVIDER: S-EPMC7725443 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Professor Sir George Alberti

Project description:Health tsars: spin or substance?: Eight health directors (“tsars”) were appointed from 1999 to 2002. Katherine Burke asked them to summarise their achievements and other people to assess their work. A ninth “tsar”, Dr Sue Roberts, was appointed in March 2003 to cover diabetes. The full text is accessible at www.bmj.com

| S-EPMC314543 | biostudies-literature

One- and two-electron reduction of triarylborane-based helical donor–acceptor compounds†‡ † This paper is dedicated to Professor Wolfgang Kaim on the occasion of his 70th birthday.‡ Electronic supplementary information (ESI) available. CCDC 2044266–2044268. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/d1sc02409d

Project description:One-electron chemical reduction of 10-(dimesitylboryl)-N,N-di-p-tolylbenzo[c]phenanthrene-4-amine (3-B(Mes)2-[4]helix-9-N(p-Tol)2) 1 and 13-(dimesitylboryl)-N,N-di-p-tolyldibenzo[c,g]phenanthrene-8-amine (3-B(Mes)2-[5]helix-12-N(p-Tol)2) 2 gives rise to monoanions with extensive delocalization over the annulated helicene rings and the boron pz orbital. Two-electron chemical reduction of 1 and 2 produces open-shell biradicaloid dianions with temperature-dependent population of the triplet states due to small singlet-triplet gaps. These results have been confirmed by single-crystal X-ray diffraction, EPR and UV/vis-NIR spectroscopy, and DFT calculations. Stepwise chemical reduction of D–π–A triarylborane-based helicenes gives the corresponding monoanions and dianions with delocalized unpaired electrons. The structures were confirmed by single crystal X-ray diffraction.

| S-EPMC8442707 | biostudies-literature

The smallest 4f-metalla-aromatic molecule of cyclo-PrB2− with Pr–B multiple bonds†‡ † Dedicated to Professor Dr W. H. E. Schwarz on his 85th birthday.‡ Electronic supplementary information (ESI) available. See https://doi.org/10.1039/d2sc02852b

Project description:The concept of metalla-aromaticity proposed by Thorn–Hoffmann (Nouv. J. Chim. 1979, 3, 39) has been expanded to organometallic molecules of transition metals that have more than one independent electron-delocalized system. Lanthanides, with highly contracted 4f atomic orbitals, are rarely found in multiply aromatic systems. Here we report the discovery of a doubly aromatic triatomic lanthanide-boron molecule PrB2− based on a joint photoelectron spectroscopy and quantum chemical investigation. Global minimum structural searches reveal that PrB2− has a C2v triangular structure with a paramagnetic triplet 3B2 electronic ground state, which can be viewed as featuring a trivalent Pr(III,f2) and B24−. Chemical bonding analyses show that this cyclo-PrB2− species is the smallest 4f-metalla-aromatic system exhibiting σ and π double aromaticity and multiple Pr–B bonding characters. It also sheds light on the formation of the rare B24− tetraanion by the high-lying 5d orbitals of the 4f-elements, completing the isoelectronic B24−, C22−, N2, and O22+ series. We report the smallest 4f-metalla-aromatic molecule of PrB2− exhibiting σ and π double aromaticity and multiple Pr–B bond characters.

| S-EPMC9430590 | biostudies-literature

Newly Emerging Strategies in Antiviral Drug Discovery: Dedicated to Prof. Dr. Erik De Clercq on Occasion of His 80th Anniversary.

Project description:Viral infections pose a persistent threat to human health. The relentless epidemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global health problem, with millions of infections and fatalities so far. Traditional approaches such as random screening and optimization of lead compounds by organic synthesis have become extremely resource- and time-consuming. Various modern innovative methods or integrated paradigms are now being applied to drug discovery for significant resistance in order to simplify the drug process. This review provides an overview of newly emerging antiviral strategies, including proteolysis targeting chimera (PROTAC), ribonuclease targeting chimera (RIBOTAC), targeted covalent inhibitors, topology-matching design and antiviral drug delivery system. This article is dedicated to Prof. Dr. Erik De Clercq, an internationally renowned expert in the antiviral drug research field, on the occasion of his 80th anniversary.

| S-EPMC8839652 | biostudies-literature

A unified strategy for the synthesis of aldohexoses by boronate assisted assembly of CH2X2 derived C1-building blocks†‡ † Dedicated to Prof. Hans-Gunther Schmalz on the occasion of his 66th birthday.‡ Electronic supplementary information (ESI) available. See DOI: https://doi.org/10.1039/d3sc03778a

Project description: Not available

| S-EPMC10510816 | biostudies-literature

Ionovoltaic electricity generation over graphene-nanoplatelets: protein-nanofibril hybrid materials†‡ † Dedicated to Professor Shigeru Yamago on the occasion of his 60th birthday.‡ Electronic supplementary information (ESI) available: SEM image of the electrode, XPS of graphite and PNFs, and AFM images of the PNFs. Electrical data and SEM images of GNP-based devices. QCMD data of GNP-based films. See DOI: https://doi.org/10.1039/d2na00388k

Project description:Continuous harvesting of electricity from the ambient environment has attracted great attention as a facile approach to green and sustainable energy. Natural water evaporation-driven electricity generators with active materials from economical and environment-friendly sources are highly sought after. Herein, we present devices made from a combination of protein nanofibrils (PNFs) and low-cost graphene nanoplatelets (GNPs) that can be employed for electricity generation, simply by partly inserting the device into evaporating standing water. The origin of the electricity generation can be explained by the ionovoltaic effect where ionic motion, driven by evaporating water, leads to movement of charge carriers in the electrically conductive GNP-phase. Moreover, the device performance can be improved by adding a small amount of salt to the active layer. A device, composed of GNP:PNF:AlCl3, produces a sustained voltage of about 0.48 V, and a current of 89 nA. Furthermore, the device can tolerate saline water, with only a modest decrease of voltage, which provides potential for harvesting electricity from both evaporating saline water and fresh water. Devices with an active layer made from protein nanofibrils, graphite nanoplatelets and salts can harvest electricity from evaporating water.

| S-EPMC9890733 | biostudies-literature

Synthesis of cyclobutane-fused chromanones via gold-mediated photocatalysis†‡ † Dedicated to Prof. Carl D. Hoff on the occasion o his 75th birthday.‡ Electronic supplementary information (ESI) available. CCDC 2283605. For ESI and crystallographic data in CIF or other electronic format see DOI: https://doi.org/10.1039/d3sc06675d

Project description: Not available

| S-EPMC10952090 | biostudies-literature

Enzyme-Instructed Peptide Assemblies Selectively Inhibit Bone Tumors.

Project description:Alkaline phosphatases (ALP) contribute to immunosuppression in solid tumors, but they, unfortunately, are "undruggable". Here we report enzyme-instructed assembly of peptides for selectively inhibiting the tumors that overexpress ALP. We developed a precursor with two parts; an amphiphilic, self-assembling peptides joined to a hydrophilic block (i.e., tyrosine phosphate). ALP, overexpressed on and in osteosarcoma cancer cells (e.g., Saos-2), cleaves the phosphates from the tyrosine residue of the precursor and triggers the self-assembly of the resulting peptides. Being selectively formed on and inside the cancer cells, the peptide assemblies induce the cancer cell death and efficiently inhibit the tumor growth in an orthotopic osteosarcoma mice model without harming normal organs. Accordingly, the peptide assemblies significantly improve the survival ratio of metastatic tumor bearing mice. Without relying on inhibiting ALP, this approach integrates enzyme reaction and molecular self-assembly for generating peptide fibrils as potential anticancer therapeutics.

| S-EPMC6758912 | biostudies-literature

MEMES: Machine learning framework for Enhanced MolEcular Screening†‡ † Dedicated to Professor N. Sathyamurthy on the occasion of his 70th birthday.‡ Electronic supplementary information (ESI) available: Tables of performance of ExactMEMES and DeepMEMES, performance comparison of MEMES with deep docking, figures of structure of top hits, distribution plots of binding affinities, distributions of molecular clusters, distributions of binding affinities of missed hits, fractions matched against the sampled percentage, protein–ligand complexes and protein–ligand interactions, and supplementary discussions and methods. See DOI: 10.1039/d1sc02783b

Project description:In drug discovery applications, high throughput virtual screening exercises are routinely performed to determine an initial set of candidate molecules referred to as “hits”. In such an experiment, each molecule from a large small-molecule drug library is evaluated in terms of physical properties such as the docking score against a target receptor. In real-life drug discovery experiments, drug libraries are extremely large but still there is only a minor representation of the essentially infinite chemical space, and evaluation of physical properties for each molecule in the library is not computationally feasible. In the current study, a novel Machine learning framework for Enhanced MolEcular Screening (MEMES) based on Bayesian optimization is proposed for efficient sampling of the chemical space. The proposed framework is demonstrated to identify 90% of the top-1000 molecules from a molecular library of size about 100 million, while calculating the docking score only for about 6% of the complete library. We believe that such a framework would tremendously help to reduce the computational effort in not only drug-discovery but also areas that require such high-throughput experiments. A novel machine learning framework based on Bayesian optimization for efficient sampling of chemical space. The framework is able to identify 90% of top-1000 hits by only sampling 6% of the complete dataset containing ∼100 million compounds.

| S-EPMC8442698 | biostudies-literature

A bis-NHC–CAAC dimer derived dicationic diradical†‡ † Dedicated to Professor Sriram Ramaswamy on the occasion of his 65th birthday.‡ Electronic supplementary information (ESI) available: Experimental details, analytical data, NMR spectra, UV/Vis spectra, X-ray crystallographic details and details of theoretical calculation. CCDC 2047110 (3Et), 2047111 (4Et), 2047113 (10Et), 2047114 (5Et), 2047112 (8Et), 2047115 (9Et), 2161952 (3Pr), 2161953 (4Pr), 2161955 (9Pr), 2161956 (3Cy), 2161957 (5Cy), 2161958 (6Cy), 2161959 (7Cy), 2204009 (5Pr). For ESI and crystallographic data in CIF or other electronic format see https://doi.org/10.1039/d2sc03937k

Project description:The isolation of carbon-centered diradicals is always challenging due to synthetic difficulties and their limited stability. Herein we report the synthesis of a trans-1,4-cyclohexylene bridged bis-NHC–CAAC dimer derived thermally stable dicationic diradical. The diradical character of this compound was confirmed by EPR spectroscopy. The variable temperature EPR study suggests the singlet state to be marginally more stable than the triplet state (2J = −5.5 cm−1 (ΔEST = 0.065 kJ mol−1)). The presence of the trans-1,4-cyclohexylene bridge is instrumental for the successful isolation of this dicationic diradical. Notably, in the case of ethylene or propylene bridged bis-NHC–CAAC dimers, the corresponding dicationic diradicals are transient and rearrange to hydrogen abstracted products. A dicationic diradical has been synthesized from the N,N′- trans-1,4-cyclohexylene bridged bis-NHC–CAAC dimer.

| S-EPMC9629079 | 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