Browse
Submit Data
Databases
API
Help

Dataset Information

30 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Developing chemically modified redox-responsive proteins as smart therapeutics.

ABSTRACT: The conditional control of protein function in response to the physiological changes of diseased cells is essential to develop smart protein therapeutics. Herein, we report a redox-responsive chemical modification of a protein by conjugating an intracellular glutathione (GSH)-cleavable ligand, NSA, onto a protein residue. We demonstrated that the NSA conjugation of Ribonuclease A (RNase A) enabled the control of the protein function by GSH in an aqueous solution and living cells, with extended applications for targeted cancer therapy using a lipid nanoparticle-based intracellular protein delivery strategy.

SUBMITTER: Tang Q

PROVIDER: S-EPMC6556230 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Developing chemically modified redox-responsive proteins as smart therapeutics.

Tang Qiao Q Wang Jianxue J Jiang Ying Y Zhang Meining M Chang Jin J Xu Qiaobing Q Mao Lanqun L Wang Ming M

Chemical communications (Cambridge, England) 20190401 35

The conditional control of protein function in response to the physiological changes of diseased cells is essential to develop smart protein therapeutics. Herein, we report a redox-responsive chemical modification of a protein by conjugating an intracellular glutathione (GSH)-cleavable ligand, NSA, onto a protein residue. We demonstrated that the NSA conjugation of Ribonuclease A (RNase A) enabled the control of the protein function by GSH in an aqueous solution and living cells, with extended a ...[more]

PMID: 30984934

Similar Datasets

Redox-Responsive Self-Assembled Chain-Shattering Polymeric Therapeutics.

Project description:We report the design and development of redox-responsive chain-shattering polymeric therapeutics (CSPTs). CSPTs were synthesized by condensation polymerization and further modified with poly(ethylene glycol) (PEG) via "Click" reaction. Size-controlled CSPT nanoparticles (NPs) were formed through nanoprecipitation with high drug loading (up to 18%); the particle size increased in a concentration dependent manner. Drug release from particles was well controlled over 48 h upon redox triggering. The anticancer efficacy of the CSPT NPs was validated both in vitro and in vivo.

| S-EPMC4486357 | biostudies-literature

Redox Responsive Copolyoxalate Smart Polymers for Inflammation and Other Aging-Associated Diseases.

Project description:Polyoxalate (POx) and copolyoxalate (CPOx) smart polymers are topics of interest the field of inflammation. This is due to their drug delivery ability and their potential to target reactive oxygen species (ROS) and to accommodate small molecules such as curcumin, vanilline, and p-Hydroxybenzyl alcohol. Their biocompatibility, ultra-size tunable characteristics and bioimaging features are remarkable. In this review we discuss the genesis and concept of oxylate smart polymer-based particles and a few innovative systemic delivery methods that is designed to counteract the inflammation and other aging-associated diseases (AADs). First, we introduce the ROS and its role in human physiology. Second, we discuss the polymers and methods of incorporating small molecule in oxalate backbone and its drug delivery application. Finally, we revealed some novel proof of concepts which were proven effective in disease models and discussed the challenges of oxylate polymers.

| S-EPMC8198274 | biostudies-literature

Printing "Smart" Inks of Redox-Responsive Organometallic Polymers on Microelectrode Arrays for Molecular Sensing.

Project description:Printing arrays of responsive spots for multiplexed sensing with electrochemical readout requires new molecules and precise, high-throughput deposition of active compounds on microelectrodes with spatial control. We have designed and developed new redox-responsive polymers, featuring a poly(ferrocenylsilane) (PFS) backbone and side groups with disulfide units, which allow an efficient and stable bonding to Au substrates, using sulfur-gold coupling chemistry in a "grafting-to" approach. The polymer molecules can be employed for area selective molecular sensing following their deposition by high-precision inkjet printing. The new PFS derivatives, which serve as "molecular inks", were characterized by 1H NMR, 13C NMR, and FTIR spectroscopies and by gel permeation chromatography. The viscosity and surface tension of the inks were assessed by rheology and pendant drop contact angle measurements, respectively. Commercial microelectrode arrays were modified with the new PFS ink by using inkjet printing in the "drop-on-demand" mode. FTIR spectroscopy, AFM, and EDX-SEM confirmed a successful, spatially localized PFS modification of the individual electrodes within the sensing cells of the microelectrode arrays. The potential application of these devices to act as an electrochemical sensor array was demonstrated with a model analyte, ascorbic acid, by using cyclic voltammetry and amperometric measurements.

| S-EPMC6790938 | biostudies-literature

Proteomic analysis of early-responsive redox-sensitive proteins in Arabidopsis.

Project description:Regulation of protein function through oxidative modification has emerged as an important molecular mechanism modulating various biological processes. Here, we report a proteomic study of redox-sensitive proteins in Arabidopsis cells subjected to H(2)O(2) treatment. Four gel-based approaches were employed, leading to the identification of four partially overlapping sets of proteins whose thiols underwent oxidative modification in the H(2)O(2)-treated cells. Using a method based on differential labeling of thiols followed by immunoprecipitation and Western blotting, five of the six selected putative redox-sensitive proteins were confirmed to undergo oxidative modification following the oxidant treatment in Arabidopsis leaves. Another method, which is based on differential labeling of thiols coupled with protein electrophoretic mobility shift assay, was adopted to reveal that one of the H(2)O(2)-sensitive proteins, a homologue of cytokine-induced apoptosis inhibitor 1 (AtCIAPIN1), also underwent oxidative modification in Arabidopsis leaves after treatments with salicylic acid or the peptide elicitor flg22, two inducers of defense signaling. The redox-sensitive proteins identified from the proteomic study are involved in various biological processes such as metabolism, the antioxidant system, protein biosynthesis and processing, and cytoskeleton organization. The identification of novel redox-sensitive proteins will be helpful toward understanding of cellular components or pathways previously unknown to be redox-regulated.

| S-EPMC3253204 | biostudies-literature

Biochemically responsive smart surface.

Project description:A design of smart surfaces responsive to biochemical analytes is demonstrated in the example of mixed monolayers of biotin/fluorocarbon. The contact angle of aqueous solutions on such surfaces decreases upon streptavidin binding and can be used in detecting this protein. The specificity of the effect is confirmed by the lack of a contact angle change by streptavidin blocked with biotin and by bovine serum albumin.

| S-EPMC2809412 | biostudies-literature

Effects of Chemically-Modified Polypyridyl Ligands on the Structural and Redox Properties of Tricarbonylmanganese(I) Complexes.

Project description:Carbonyl complexes with manganese(I) as the central metal are very attractive catalysts. The introduction of redox-active ligands, such as quinones and methyl viologen analogs into these catalysts, would be expected to lead to superior catalyst performances, since they can function as excellent electron carriers. In this study, we synthesized four tricarbonylmanganese(I) complexes containing typical bidentate polypyridyl ligands, including 1,10-phenanthroline (phen) and 2,2'-bipyridine (bpy) frameworks bound to redox-active ortho-quinone/catechol or methyl viologen-like units. The molecular structures of the resulting complexes were determined by X-ray crystallography to clarify their steric features. As expected from the infrared (IR) data, three CO ligands for each complex were coordinated in the facial configuration around the central manganese(I) atom. Additionally, the structural parameters were found to differ significantly between the quinone/catechol units. Electrochemical analysis revealed some differences between them and their reference complexes, namely [MnBr(CO)3(phen)] and [MnBr(CO)3(bpy)]. Notably, interconversions induced by two-electron/two-proton transfers between the quinone and catechol units were observed in the phenanthroline-based complexes. This work indicated that the structural and redox properties in tricarbonylmanganese(I) complexes were significantly affected by chemically modified polypyridyl ligands. A better understanding of structures and redox behaviors of the present compounds would facilitate the design of new manganese complexes with enhanced properties.

| S-EPMC7765023 | biostudies-literature

Smart Material Hydrogel Transfer Devices Fabricated with Stimuli-Responsive Silk-Elastin-Like Proteins.

Project description:Three-dimensional organoid tissue culture models are a promising approach for the study of biological processes including diseases. Advances in these tissue culture technologies improve in vitro analysis compared to standard 2D cellular approaches and are more representative of the physiological environment. However, a major challenge associated with organoid systems stems from the laborious processing involved in the analysis of large numbers of organoids. Here the design, characterization, and application of silk-elastin-like protein-based smart carrier arrays for processing organoids is presented. Fabrication of hydrogel-based carrier systems at room temperature result in organized arrays of organoids that maintain tissue culture plate orientation and could be processed simultaneously for histology. The system works by transfer of the organoids to the hydrogel arrays after which the material is subjected to 65 °C to induce hydrogel contraction to secure the organoids, resulting in multisample constructs and allowing for placement on a microscope slide. Histological processing and immunostaining of these arrayed cerebral organoids analyzed within the contracted silk-elastin-like proteins (SELP) show retention of native organoid features compared to controls without the hydrogel carrier system, thus avoiding any artifacts. These SELP carriers present a useful approach for improving efficiency of scaled organoid screening and processing.

| S-EPMC7466789 | biostudies-literature

Smart Targeting To Improve Cancer Therapeutics.

Project description:Cancer is the second largest cause of death worldwide with the number of new cancer cases predicted to grow significantly in the next decades. Biotechnology and medicine can and should work hand-in-hand to improve cancer diagnosis and treatment efficacy. However, success has been frequently limited, in particular when treating late-stage solid tumors. There still is the need to develop smart and synergistic therapeutic approaches to achieve the synthesis of strong and effective drugs and delivery systems. Much interest has been paid to the development of smart drug delivery systems (drug-loaded particles) that utilize passive targeting, active targeting, and/or stimulus responsiveness strategies. This review will summarize some main ideas about the effect of each strategy and how the combination of some or all of them has shown to be effective. After a brief introduction of current cancer therapies and their limitations, we describe the biological barriers that nanoparticles need to overcome, followed by presenting different types of drug delivery systems to improve drug accumulation in tumors. Then, we describe cancer cell membrane targets that increase cellular drug uptake through active targeting mechanisms. Stimulus-responsive targeting is also discussed by looking at the intra- and extracellular conditions for specific drug release. We include a significant amount of information summarized in tables and figures on nanoparticle-based therapeutics, PEGylated drugs, different ligands for the design of active-targeted systems, and targeting of different organs. We also discuss some still prevailing fundamental limitations of these approaches, eg, by occlusion of targeting ligands.

| S-EPMC6826196 | biostudies-literature

Digging for Stress-Responsive Cell Wall Proteins for Developing Stress-Resistant Maize.

Project description:As a vital component of plant cell walls, proteins play important roles in stress response by modifying the structure of cell walls and involving in the wall integrity signaling pathway. Recently, we have critically reviewed the predictors, databases, and cross-referencing of the subcellular locations of possible cell wall proteins (CWPs) in plants (Briefings in Bioinformatics 2018;19:1130-1140). Here, we briefly introduce strategies for isolating CWPs during proteomic analysis. Taking maize (Zea mays) as an example, we retrieved 1873 probable maize CWPs recorded in the UniProt KnowledgeBase (UniProtKB). After curation, 863 maize CWPs were identified and classified into 59 kinds of protein families. By referring to gene ontology (GO) annotations and gene differential expression in the Expression Atlas, we have highlighted the potential of CWPs acting in the front line of defense against biotic and abiotic stresses. Moreover, the analysis results of cis-acting elements revealed the responsiveness of the genes encoding CWPs toward phytohormones and various stresses. We suggest that the stress-responsive CWPs could be promising candidates for applications in developing varieties of stress-resistant maize.

| S-EPMC7546335 | biostudies-literature

Dialysis Preparation of Smart Redox and Acidity Dual Responsive Tea Polyphenol Functionalized Calcium Phosphate Nanospheres as Anticancer Drug Carriers.

Project description:Large-scale preparation of biocompatible drug delivery systems with targeted recognition and controlled release properties has always been attractive. However, this strategy has been constrained by a lot of design challenges, such as complicated steps and premature drug release. Herein, in this paper, we address these problems by a facile in situ mineralization method, which synthesizes biodegradable tea polyphenol coated monodisperse calcium phosphate nanospheres using for targeted and controlled delivery of doxorubicin. Dialysis diffusion method was used to control ion release to form mineralized nanospheres. The polyphenol coatings and calcium phosphate used in this work could be biodegraded by intracellular glutathione and acidic microenvironment, respectively, resulting the release of encapsulated drug. According to confocal fluorescence microscopy, and cytotoxicity experiments, the prepared tea polyphenol functionalized, doxorubicin loaded calcium phosphate nanospheres were confirmed to have highly efficient internalization and obvious cell killing effect on target tumor cells, but not normal cells. Our results suggest that these tea polyphenols functionalized calcium phosphate nanospheres are promising vehicles for controlled release of an anticancer drug in cancer therapy.

| S-EPMC7179473 | 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