Browse
Submit Data
Databases
API
Help

Dataset Information

15 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Probing biotin receptors in cancer cells with rationally designed fluorogenic squaraine dimers.

ABSTRACT: Fluorogenic probes enable imaging biomolecular targets with high sensitivity and maximal signal-to-background ratio under non-wash conditions. Here, we focus on the molecular design of biotinylated dimeric squaraines that undergo aggregation-caused quenching in aqueous media through intramolecular H-type dimerization, but turn on their fluorescence in apolar environment due to target-mediated disaggregation. Our structure-property study revealed that depending on the linkers used to connect the squaraine dyes, different aggregation patterns could be obtained (intramolecular dimerization versus intermolecular aggregation) leading to different probing efficiencies. Using a relatively short l-lysine linker we developed a bright fluorogenic probe, Sq2B, displaying only intramolecular dimerization-caused quenching properties in aqueous media. The latter was successfully applied for imaging biotin receptors, in particular sodium-dependent multivitamin transporter (SMVT), which are overexpressed at the surface of cancer cells. Competitive displacement with SMVT-targets, such as biotin, lipoic acid or sodium pantothenate, showed Sq2B targeting ability to SMVT. This fluorogenic probe for biotin receptors could distinguish cancer cells (HeLa and KB) from model non-cancer cell lines (NIH/3T3 and HEK293T). The obtained results provide guidelines for development of new dimerization-based fluorogenic probes and propose bright tools for imaging biotin receptors, which is particularly important for specific detection of cancer cells.

SUBMITTER: Fam KT

PROVIDER: S-EPMC8163205 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Rationally designed fluorogenic protease reporter visualizes spatiotemporal dynamics of apoptosis in vivo.

Project description:Fluorescence resonance energy transfer-based reporters have been widely used in imaging cell signaling; however, their in vivo application has been handicapped because of poor signal. Although fluorogenic reporters overcome this problem, no such reporter of proteases has been demonstrated for in vivo imaging. Now we have redesigned an infrared fluorescent protein so that its chromophore incorporation is regulated by protease activity. Upon protease activation, the infrared fluorogenic protease reporter becomes fluorescent with no requirement of exogenous cofactor. To demonstrate biological applications, we have designed an infrared fluorogenic executioner-caspase reporter, which reveals spatiotemporal coordination between cell apoptosis and embryonic morphogenesis, as well as dynamics of apoptosis during tumorigenesis in Drosophila. The designed scaffold may be used to engineer reporters of other proteases with specific cleavage sequence.

| S-EPMC4371907 | biostudies-other

Nature of intermolecular interaction in squaraine dimers.

Project description:Squaraine dyes are known for their particular optical properties. They exhibit intense photochemically stable fluorescence in usually (near) infra red region that can be quenched by intermolecular interactions. Moreover, even the centrosymmetric dyes feature non-zero second harmonic generation upon aggregation. Therefore, the detailed knowledge of the squaraine dye interaction nature both in homogenic aggregates and with other species present in the environment can be of importance for the design of new materials of desired properties. In the present study, interaction in squaraine dimers is investigated with quantum chemistry tools. Four structures: two stacked and two hydrogen-bonded are analyzed in terms of supermolecular approach and symmetry-adapted perturbation theory. MP2C/aug-cc-pVTZ supermolecular calculations confirm the particular stability of the stacked dimers and the favoured dispersion attraction for the long-displaced system.

| S-EPMC7665223 | biostudies-literature

Rationally Designed Ruthenium Complexes for Breast Cancer Therapy.

Project description:Since the discovery of the anticancer potential of ruthenium-based complexes, several species were reported as promising candidates for the treatment of breast cancer, which accounts for the greatest number of new cases in women every year worldwide. Among these ruthenium complexes, species containing bioactive ligand(s) have attracted increasing attention due to their potential multitargeting properties, leading to anticancer drug candidates with a broader range of cellular targets/modes of action. This review of the literature aims at providing an overview of the rationally designed ruthenium-based complexes that have been reported to date for which ligands were carefully selected for the treatment of hormone receptor positive breast cancers (estrogen receptor (ER+) or progesterone receptor (PR+)). In addition, this brief survey highlights some of the most successful examples of ruthenium complexes reported for the treatment of triple negative breast cancer (TNBC), a highly aggressive type of cancer, regardless of if their ligands are known to have the ability to achieve a specific biological function.

| S-EPMC7024301 | biostudies-literature

A rationally designed genotoxin that selectively destroys estrogen receptor-positive breast cancer cells.

Project description:We describe a novel strategy to increase the selective toxicity of genotoxic compounds. The strategy involves the synthesis of bifunctional molecules capable of forming DNA adducts that have high affinity for specific proteins in target cells. It is proposed that the association of such proteins with damaged sites in DNA can compromise protein function and/or DNA repair resulting in increased toxicity. We describe the synthesis of a bifunctional compound consisting of an aniline mustard linked to the 7alpha position of estradiol. This novel compound can form covalent DNA adducts that have high affinity for the estrogen receptor. Breast cancer cells that express high levels of the estrogen receptor showed increased sensitivity to the cytotoxic effects of the new compound.

| S-EPMC4095803 | biostudies-literature

Probing strigolactone perception mechanisms with rationally designed small-molecule agonists stimulating germination of root parasitic weeds.

Project description:The development of potent strigolactone (SL) agonists as suicidal germination inducers could be a useful strategy for controlling root parasitic weeds, but uncertainty about the SL perception mechanism impedes real progress. Here we describe small-molecule agonists that efficiently stimulate Phelipanchce aegyptiaca, and Striga hermonthica, germination in concentrations as low as 10-8 to 10-17 M. We show that full efficiency of synthetic SL agonists in triggering signaling through the Striga SL receptor, ShHTL7, depends on the receptor-catalyzed hydrolytic reaction of the agonists. Additionally, we reveal that the stereochemistry of synthetic SL analogs affects the hydrolytic ability of ShHTL7 by influencing the probability of the privileged conformations of ShHTL7. Importantly, an alternative ShHTL7-mediated hydrolysis mechanism, proceeding via nucleophilic attack of the NE2 atom of H246 to the 2'C of the D-ring, is reported. Together, our findings provide insight into SL hydrolysis and structure-perception mechanisms, and potent suicide germination stimulants, which would contribute to the elimination of the noxious parasitic weeds.

| S-EPMC9271048 | biostudies-literature

Rationally designed treatment for metastatic colorectal cancer: current drug development strategies.

Project description:The therapeutic landscape of metastatic colorectal cancer (mCRC) has changed substantially with the emergence of new molecularly targeted agents (MTA) used as single agents or alongside standard chemotherapy. The use of these MTAs extended the overall survival of patients with mCRC to a level that current chemotherapeutics alone could not achieve. In addition, improvement in surgical techniques and ablation modalities offer cure to a limited subset of patients with mCRC and MTAs have been found to have a significant role here too, as they aid resectability. However, for the majority of patients, mCRC remains an invariably incurable disease necessitating continued courses of combined treatment modalities. During the course of these treatments, either cytotoxic or biological, cancer cells maintain their ability to acquire mitogenic mutations which render them resistant to treatment. Key challenges remain to identify appropriate subsets of patients who will most likely benefit from these new MTAs and effectively select these based on validated biomarkers. Moreover, better knowledge of the biology of colorectal cancer and the mechanisms via which it bypasses blockade of known signalling pathways will help us design better and more rational sequencing of these treatments, so that we can maximise the survivorship of mCRC patients. This review outlines treatment strategies for known molecular alterations with new MTAs and highlights some promising strategies.

| S-EPMC4130836 | biostudies-other

Rationally designed logic integration of regulatory signals in mammalian cells.

Project description:Molecular-level information processing is essential for 'smart' in vivo nanosystems. Natural molecular computing, such as the regulation of messenger RNA (mRNA) synthesis by special proteins called transcription factors, has inspired engineered systems that can control the levels of mRNA with certain combinations of transcription factors. Here, we show an alternative approach to achieving general-purpose control of mRNA and protein levels by logic integration of transcription factor input signals in mammalian cells. The transcription factors regulate synthetic genes coding for small regulatory RNAs (called microRNAs), which, in turn, control the mRNA of interest (the output) via an RNA interference pathway. The simplicity of these modular interactions makes it possible, in theory, to implement any arbitrary logic relation between the transcription factors and the output. We construct, test and optimize increasingly complex circuits with up to three transcription factor inputs, establishing a platform for in vivo molecular computing.

| S-EPMC2934882 | biostudies-literature

Bovine serum albumin nanoparticles with fluorogenic near-IR-emitting squaraine dyes.

Project description:Two squaraine (SQ) dyes, N-propanesulfonate-benzothiazolium squaraine (SQ-1) and N-propanesulfonate-benzoindolium squaraine (SQ-2), were synthesized with sulfonate groups to increase water solubility. Both dyes are almost nonfluorescent in aqueous solution with fluorescent quantum yields of 0.03, but exhibited fluorescence enhancement after noncovalently binding with bovine serum albumin (BSA). Upon addition of BSA, the fluorescence intensity increased by ca. a factor of 10, along with a 10-fold extension in the fluorescence lifetime. SQ-1 and SQ-2 interacted with BSA efficiently and appeared to show a preference for binding at site II, which involves combinational effects of electrostatic and hydrophobic interactions. The fluorogenic squaraine dyes were then used to label BSA, forming BSA-based nanoparticles (NPs) through noncovalent binding. The resulting BSA-SQ NPs exhibited enhanced near-IR fluorescence and reduced aggregation of the squaraine moiety. The BSA-SQ NPs were used for cell incubation and bioimaging studies. Confocal fluorescent images were obtained for HCT 116 cells incubated with the BSA-SQ NPs and LysoSensor Green, demonstrating the utility of the NP probes for intracellular imaging. This strategy ovecomes the generally low fluorescence emission of SQ dyes in water and aggregation-reduced fluorescence, providing a versatile strategy for sensing and imaging in biological environments.

| S-EPMC3820157 | biostudies-literature

A Rationally Designed ICAM1 Antibody Drug Conjugate for Pancreatic Cancer.

Project description:Outcomes for pancreatic cancer (PC) patients remain strikingly poor with a 5-year survival of less than 8% due to the lack of effective treatment modalities. Here, a novel precision medicine approach for PC treatment is developed, which is composed of a rationally designed tumor-targeting ICAM1 antibody-drug conjugate (ADC) with optimized chemical linker and cytotoxic payload, complemented with a magnetic resonance imaging (MRI)-based molecular imaging approach to noninvasively evaluate the efficiency of ICAM1 ADC therapy. It is shown that ICAM1 is differentially overexpressed on the surface of human PC cells with restricted expression in normal tissues, enabling ICAM1 antibody to selectively recognize and target PC tumors in vivo. It is further demonstrated that the developed ICAM1 ADC induces potent and durable tumor regression in an orthotopic PC mouse model. To build a precision medicine, an MRI-based molecular imaging approach is developed that noninvasively maps the tumoral ICAM1 expression that can be potentially used to identify ICAM1-overexpressing PC patients. Collectively, this study establishes a strong foundation for the development of a promising ADC to address the critical need in the PC patient care.

| S-EPMC7740099 | biostudies-literature

A rationally designed histone deacetylase inhibitor with distinct antitumor activity against ovarian cancer.

Project description:Histone deacetylase inhibitors (HDACIs) are a class of antineoplastic agents previously demonstrating preclinical chemosensitizing activity against drug-resistant cancer cells and mouse xenografts. However, whereas clinical studies have shown efficacy against human hematologic malignancies, solid tumor trials have proved disappointing. We previously developed a novel HDACI, "OSU-HDAC42," and herein examine its activity against ovarian cancer cell lines and xenografts. OSU-HDAC42, (i) unlike most HDACIs, elicited a more than five-fold increase in G(2)-phase cells, at 2.5 microM, with G(2) arrest followed by apoptosis; (ii) at 1.0 microM, completely repressed messenger RNA expression of the cell cycle progression gene cdc2; (iii) at low doses (0.25-1.0 microM for 24 hours), induced tumor cell epithelial differentiation, as evidenced by morphology changes and a more than five-fold up-regulation of epithelium-specific cytokeratins; (iv) potently abrogated the growth of numerous ovarian cancer cells, with IC(50) values of 0.5 to 1.0 microM, whereas also remaining eight-fold less toxic (IC(50) of 8.6 microM) to normal ovarian surface epithelial cells; and (v) chemosensitizated platinum-resistant mouse xenografts to cisplatin. Compared with the clinically approved HDACI suberoylanilide hydroxamic acid (vorinostat), 1.0 microM OSU-HDAC42 was more biochemically potent (i.e., enzyme-inhibitory), as suggested by greater gene up-regulation and acetylation of both histone and nonhistone proteins. In p53-dysfunctional cells, however, OSU-HDAC42 was two- to eight-fold less inductive of p53-regulated genes, whereas also having a two-fold higher IC(50) than p53-functional cells, demonstrating some interaction with p53 tumor-suppressive cascades. These findings establish OSU-HDAC42 as a promising therapeutic agent for drug-resistant ovarian cancer and justify its further investigation.

| S-EPMC2685444 | 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