Browse
Submit Data
Databases
API
Help

Dataset Information

23 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Bioorthogonal release of anticancer drugs via gold-triggered 2-alkynylbenzamide cyclization.

ABSTRACT: Metal-based uncaging of biomolecules has become an emerging approach for in vivo applications, which is largely due to the advantageous bioorthogonality of abiotic transition metals. Adding to the library of metal-cleavable protecting groups, this work introduces the 2-alkynylbenzamide (Ayba) moiety for the gold-triggered release of secondary amines under mild and physiological conditions. Studies were further performed to highlight some intrinsic benefits of the Ayba protecting group, which are (1) its amenable nature to derivatization for manipulating prodrug properties, and (2) its orthogonality with other commonly used transition metals like palladium and ruthenium. With a focus on highlighting its application for anticancer drug therapies, this study successfully shows that gold-triggered conversion of Ayba-protected prodrugs into bioactive anticancer drugs (i.e. doxorubicin, endoxifen) can proceed effectively in cell-based assays.

SUBMITTER: Vong K

PROVIDER: S-EPMC8162444 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Photoregulated release of caged anticancer drugs from gold nanoparticles.

Project description:An anticancer drug (5-fluorouracil) was conjugated to the surface of gold nanoparticles through a photocleavable o-nitrobenzyl linkage. In this system, the particle serves as both cage and carrier for the therapeutic, providing a nontoxic conjugate that effectively releases the payload upon long wavelength UV irradiation.

| S-EPMC2673701 | biostudies-literature

Epirubicin-loaded marine carrageenan oligosaccharide capped gold nanoparticle system for pH-triggered anticancer drug release.

Project description:Gold nanoparticles (AuNPs) and the pH stimuli-responsive drug delivery system have been extensively applied in cancer treatment. Carrageenan derived from marine red algae shows a promising application prospect for drug delivery as a nanomaterial for its biodegradability, abundance, and non-toxicity. Carrageenan oligosaccharide (CAO) was used as a biocompatible reductant for green synthesis of CAO-AuNPs, and the obtained CAO-AuNPs were further used as a delivery system for pH-triggered delivery of epirubicin (EPI). The EPI-CAO-AuNPs were demonstrated to be spherical and homogeneous with mean diameter of 141 ± 6 nm by means of electron microscopy and Malvern particle size analyzer. Results showed that the release of EPI from EPI-CAO-AuNPs was significant under acidic condition that simulated cancer environment, while it was negligible under physiological pH in vitro. Confocal laser scanning microscope and flow cytometry analysis showed that EPI-CAO-AuNPs were localized in cellular nucleus and induced more apoptosis of HCT-116 and HepG2 cells than free EPI. A new pH-triggered anticancer drug release was achieved by EPI-CAO-AuNPs system for the first time. The developed EPI-CAO-AuNPs nanosystem shows a promising prospect for pH-triggered delivery of antitumor drugs, and our work provides a new idea for targeted drug delivery by using biocompatible marine carbohydrates as nanomaterial.

| S-EPMC6494808 | biostudies-other

Remotely triggered liposome release by near-infrared light absorption via hollow gold nanoshells.

Project description:An elusive goal for systemic drug delivery is to provide both spatial and temporal control of drug release. Liposomes have been evaluated as drug delivery vehicles for decades, but their clinical significance has been limited by slow release or poor availability of the encapsulated drug. Here we show that near-complete liposome release can be initiated within seconds by irradiating hollow gold nanoshells (HGNs) with a near-infrared (NIR) pulsed laser. Our findings reveal that different coupling methods such as having the HGNs tethered to, encapsulated within, or suspended freely outside the liposomes, all triggered liposome release but with different levels of efficiency. For the underlying content release mechanism, our experiments suggest that the microbubble formation and collapse due to the rapid temperature increase of the HGN is responsible for liposome disruption, as evidenced by the formation of solid gold particles after the NIR irradiation and the coincidence of a laser power threshold for both triggered release and pressure fluctuations in the solution associated with cavitation. These effects are similar to those induced by ultrasound and our approach is conceptually analogous to the use of optically triggered nano-"sonicators" deep inside the body for drug delivery. We expect HGNs can be coupled with any nanocarriers to promote spatially and temporally controlled drug release. In addition, the capability of external HGNs to permeabilize lipid membranes can facilitate the cellular uptake of macromolecules including proteins and DNA and allow for promising applications in gene therapy.

| S-EPMC2593911 | biostudies-literature

Bioorthogonal release of sulfonamides and mutually orthogonal liberation of two drugs.

Project description:Sulfonamide derivatives have been used in pharmaceutics for decades. Here we report a new approach to release sulfonamides efficiently using a bioorthogonal reaction of sulfonyl sydnonimines and dibenzoazacyclooctyne (DIBAC). The second-order rate constant of the cycloaddition reaction can be up to 0.62 M-1 s-1, and the reactants are highly stable under physiological conditions. Most significantly, we also discovered the mutual orthogonality between the sydnonimine-DIBAC and benzonorbornadiene-tetrazine cycloaddition pairs, which can be used for selective and simultaneous liberation of sulfonamide and primary amine drugs.

| S-EPMC6314811 | biostudies-literature

Unraveling Tetrazine-Triggered Bioorthogonal Elimination Enables Chemical Tools for Ultrafast Release and Universal Cleavage.

Project description:Recent developments in bond cleavage reactions have expanded the scope of bioorthogonal chemistry beyond click ligation and enabled new strategies for probe activation and therapeutic delivery. These applications, however, remain in their infancy, with further innovations needed to achieve the efficiency required for versatile and broadly useful tools in vivo. Among these chemistries, the tetrazine/ trans-cyclooctene click-to-release reaction has exemplary kinetics and adaptability but achieves only partial release and is incompletely understood, which has limited its application. Investigating the mechanistic features of this reaction's performance, we discovered profound pH sensitivity, exploited it with acid-functionalized tetrazines that both enhance and markedly accelerate release, and ultimately uncovered an unexpected dead-end isomer as the reason for poor release. Implementing facile methods to prevent formation of this dead end, we have achieved exceptional efficiency, with essentially complete release across the full scope of physiologic pH, potentiating drug-delivery strategies and expanding the dynamic range of bioorthogonal on/off control.

| S-EPMC5857921 | biostudies-literature

Gold-Catalyzed Cyclization of Yndiamides with Isoxazoles via α-Imino Gold Fischer Carbenes.

Project description:Gold catalysis is an important method for alkyne functionalization. Here we report the gold-catalyzed formal [3+2] aminative cyclization of yndiamides and isoxazoles in a direct synthesis of polysubstituted diaminopyrroles, which are important motifs in drug discovery. Key to this process is the formation, and subsequent cyclization, of an α-imino gold Fischer carbene, which represents a new type of gold carbene intermediate. The reaction proceeds rapidly under mild conditions, with high regioselectivity being achieved by introducing a subtle steric bias between the nitrogen substituents on the yndiamide. DFT calculations revealed that the key to this regioselectivity was the interconversion of isomeric gold keteniminiun ions via a low-barrier π-complex transition state, which establishes a Curtin-Hammett scenario for isoxazole addition. By using benzisoxazoles as substrates, the reaction outcome could be switched to a formal [5+2] cyclization, leading to 1,4-oxazepines.

| S-EPMC10947298 | biostudies-literature

Drug-free albumin-triggered sensitization of cancer cells to anticancer drugs.

Project description:Chemosensitization strategies have been used to sensitize cancer cells to conventional drugs, but their utility is often obstructed by additional off-target toxicity, limited access to intracellular targets and heterogeneous tumor pathogenesis. To address these challenges, we rationally developed a drug-free human serum albumin (HSA)-based therapeutic (KH-1) that functions extracellularly and exhibits pleiotropic effect on multiple intracellular signaling pathways. It is a two-step touch-trigger system that consists of a pretargeting anchor on surface receptor CD20 (anti-CD20 Fab' conjugated with a morpholino oligonucleotide 1) and a CD20 clustering actuator (HSA grafted with multiple copies of complementary morpholino oligonucleotide 2). The extracellular actuation by surface CD20 crosslinking boosts robust activations of numerous intracellular responses, and promotes cancer cell susceptibility to various anticancer drugs, including docetaxel (microtubule stabilizer), gemcitabine (nucleoside analogue) and GDC-0980 (PI3K/mTOR inhibitor). The broad applicability of KH-1 is demonstrated to result from simultaneous inhibition of survival pathways and augmentation of apoptotic pathways. In addition, KH-1 covalently conjugated with anthracycline anticancer agent, epirubicin, integrates the advantages of both chemosensitization function and improved intracellular drug delivery in a single system and takes effect on the same cell. Therefore, in the present study, we have provided mechanistic demonstration that crosslinking of surface receptors can be leveraged to elicit chemosensitization.

| S-EPMC6317733 | biostudies-literature

Chemically triggered crosslinking with bioorthogonal cyclopropenones.

Project description:We report a proximity-driven crosslinking strategy featuring bioorthogonal cyclopropenones. These motifs react with phosphines to form electrophilic ketene-ylides. Such intermediates can be trapped by neighboring proteins to form covalent adducts. Successful crosslinking was achieved using a model split reporter, and the rate of crosslinking could be tuned using different phosphine triggers. We further demonstrated that the reaction can be performed in cell lysate. Based on these features, we anticipate that cyclopropenones will enable unique studies of protein-protein and other biomolecule interactions.

| S-EPMC7501174 | biostudies-literature

Synthesis of (+/-)-3H-epivincamine via a Rh(II)-triggered cyclization/cycloaddition cascade.

Project description:A synthesis of (+/-)-3H-epivincamine is reported. Important steps include (1) a Rh(II)-catalyzed intramolecular [3+2]-cycloaddition of an alpha-diazo indolo amide, (2) a reductive ring opening of the cycloadduct, (3) a decarboethoxylation reaction, and (4) a base-induced keto-amide ring contraction.

| S-EPMC2587099 | biostudies-literature

Enantioselective total synthesis of (-)-nardoaristolone B via a gold(I)-catalyzed oxidative cyclization.

Project description:The first enantioselective total synthesis of (-)-nardoaristolone B is accomplished by the implementation of an enantio- and diastereoselective copper(I)-catalyzed conjugate addition/enolate trapping sequence and a gold(I)-catalyzed oxidative cyclization (intermolecular oxidant), employed for the first time in total synthesis.

| S-EPMC4322447 | biostudies-other

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