31 results on '"Tanasova M"'
Search Results
2. Multicolor GLUT5-permeable fluorescent probes for fructose transport analysis.
- Author
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Begoyan, V. V., Weseliński, Ł. J., Xia, S., Fedie, J., Kannan, S., Ferrier, A., Rao, S., and Tanasova, M.
- Subjects
PERMEABILITY measurement ,FLUORESCENT probes ,CARBOHYDRATE analysis - Abstract
The specificity of carbohydrate transporters towards their substrates poses a significant challenge for the development of molecular probes to monitor sugar uptake in cells for biochemical and biomedical applications. Herein we report a new set of coumarin-based fluorescent sugar conjugates applicable for the analysis of fructose uptake due to their free passage through the fructose-specific transporter GLUT5. The reported probes cover a broad range of the fluorescence spectrum providing essential tools for the evaluation of fructose transport capacity in live cells. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
3. Quantification of pyrophosphate as a universal approach to determine polymerase activity and assay polymerase inhibitors.
- Author
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Malvezzi, S., Sturla, S.J., and Tanasova, M.
- Subjects
- *
PYROPHOSPHATES , *DNA polymerases , *ENZYME inhibitors , *NUCLEIC acid synthesis , *TUMOR lysis syndrome , *CANCER chemotherapy , *CELL-mediated cytotoxicity , *DNA synthesis - Abstract
The importance of DNA polymerases in biology and biotechnology, and their recognition as potential therapeutic targets, drives development of methods for deriving kinetic characteristics of polymerases and their propensity to perform polynucleotide synthesis over modified DNA templates. Among various polymerases, translesion synthesis (TLS) polymerases enable cells to avoid the cytotoxic stalling of replicative DNA polymerases at chemotherapy-induced DNA lesions, thereby leading to drug resistance. Identification of TLS inhibitors to overcome drug-resistance necessitates the development of appropriate high-throughput assays. Since polymerase-mediated DNA synthesis involves the release of inorganic pyrophosphate (PPi), we established a universal and fast method for monitoring the progress of DNA polymerases based on the quantification of PPi with a fluorescence-based assay that we coupled to in vitro primer extension reactions. The established assay has a nanomolar detection limit in PPi and enables the evaluation of single nucleotide incorporation and DNA synthesis progression kinetics. The results demonstrated that the developed assay is a reliable method for monitoring TLS and identifying nucleoside and nucleotide-based TLS inhibitors. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
4. Turn-on Rhodamine Glycoconjugates Enable Real-Time GLUT Activity Monitoring in Live Cells and In Vivo.
- Author
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Nyansa MMS, Oronova A, Gora N, Geborkoff MR, Ostlund NR, Fritz DR, Werner T, and Tanasova M
- Abstract
The direct relationship between facilitative glucose transporters (GLUTs) and metabolic diseases opens new avenues for sensing metabolic deregulations and drives the development of molecular probes for GLUT-targeted detection of metabolic diseases. Radiotracer-based molecular imaging probes have been effectively utilized in reporting alterations in sugar uptake as an indication of metabolic deregulations, cancer development, or inflammation. Progress in developing fluorophore-based tools facilitated GLUT-specific analyses using more accessible fluorescence-based instrumentation. However, restrictions on the emission range of fluorophores and the requirement for substantial post-treatments to reduce background fluorescence have brought to light the critical directions for improvement of the technology for broader use in screening applications. Here we present turn-on GLUT activity reporters activated upon cells' internalization. We demonstrate a specific delivery of a sizable rhodamine B fluorophore through GLUT5 and showcase a stringent requirement in conjugate structure for maintaining a GLUT-specific uptake. With the turn-on GLUT probes, we demonstrate the feasibility of high-throughput fluorescence microscopy and flow cytometry-based GLUT activity screening in live cells and the probes' applicability for assessing sugar uptake alterations in vivo ., Competing Interests: The authors declare no competing financial interest.
- Published
- 2023
- Full Text
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5. Highly Sensitive Cyanine Dyes for Rapid Sensing of NAD(P)H in Mitochondria and First-Instar Larvae of Drosophila melanogaster .
- Author
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Arachchige DL, Dwivedi SK, Jaeger S, Olowolagba AM, Mahmoud M, Tucker DR, Fritz DR, Werner T, Tanasova M, Luck RL, and Liu H
- Subjects
- Animals, Fluorescent Dyes chemistry, Cisplatin, Mitochondria, Drosophila melanogaster, NAD chemistry
- Abstract
We have developed two highly sensitive cyanine dyes, which we refer to as probes A and B . These dyes are capable of quick and sensitive sensing of NAD(P)H. The dyes were fabricated by connecting benzothiazolium and 2,3-dimethylnaphtho[1,2- d ]thiazol-3-ium units to 3-quinolinium through a vinyl bond. In the absence of NAD(P)H, both probes have low fluorescence and absorption peaks at 370 and 400 nm, correspondingly. This is because of their two electron-withdrawing acceptor systems with high charge densities. However, when NAD(P)H reduces the probes' electron-withdrawing 3-quinolinium units to electron-donating 1,4-dihydroquinoline units, the probes absorb at 533 and 535 nm and fluoresce at 572 and 586 nm for A and B correspondingly. This creates well-defined donor-π-acceptor cyanine dyes. We successfully used probe A to monitor NAD(P)H levels in live cells during glycolysis, under hypoxic conditions induced by CoCl
2 treatment and after treatment with cancer drugs, including cisplatin, camptothecin, and gemcitabine. Probe A was also employed to visualize NAD(P)H in Drosophila melanogaster first-instar larvae. We observed an increase in NAD(P)H levels in A549 cancer cells both under hypoxic conditions and after treatment with cancer drugs, including cisplatin, camptothecin, and gemcitabine.- Published
- 2023
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6. Discrimination of GLUTs by Fructose Isomers Enables Simultaneous Screening of GLUT5 and GLUT2 Activity in Live Cells.
- Author
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Gora N, Weselinski LJ, Begoyan VV, Cooper A, Choe JY, and Tanasova M
- Subjects
- Animals, Biological Transport, Cell Line, Tumor, Glucose Transporter Type 5 metabolism, Mammals metabolism, Fructose metabolism, Glucose metabolism
- Abstract
Facilitative carbohydrate transporters (GLUTs, SLC2 gene family) are transmembrane proteins transporting hexoses and other sugars based on cellular metabolic demands. While a direct link between GLUTs and metabolic disorders has framed them as important biological and medicinal targets, targeting disease-relevant GLUTs remains challenging. In this study, we aimed to identify substrate-GLUT interactions that would discriminate between major fructose transporters. We examined the uptake distribution for conformational and configurational isomers of fructose using the corresponding conformationally locked fluorescently labeled mimetics as probes for assessing GLUT preferences in real time. Through comparative analysis of the uptake of the probes in the yeast-based single GLUT expression systems and the multi-GLUT mammalian cell environment, we established the ability of fructose transporters to discriminate between fructose conformers and epimers. We demonstrated that recreating the conformational and configurational mixture of fructose with molecular probes allows for the specific probe distribution, with fructofuranose mimetic being taken up preferentially through GLUT5 and β-d-fructopyranose mimetic passing through GLUT2. The uptake of α-d-fructopyranose mimetic was found to be independent of GLUT5 or GLUT2. The results of this study provide a new approach to analyzing GLUT5 and GLUT2 activity in live cells, and the findings can be used as a proof-of-concept for multi-GLUT activity screening in live cells. The research also provides new knowledge on substrate-GLUT interactions and new tools for monitoring alterations in GLUT activities.
- Published
- 2023
- Full Text
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7. Late-Stage Functionalization through Click Chemistry Provides GLUT5-Targeting Glycoconjugate as a Potential PET Imaging Probe.
- Author
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Oronova A and Tanasova M
- Subjects
- Humans, Biological Transport, Cell Line, Tumor, Positron-Emission Tomography methods, Fructose metabolism, Click Chemistry
- Abstract
The targeting of facilitative sugar transporters (GLUTs) has been utilized in the development of tools for diagnostics and therapy. The interest in this area is promoted by the phenomenon of alterations in cellular metabolic processes that are linked to multitudes of metabolic disorders and diseases. However, nonspecific targeting (e.g., glucose-transporting GLUTs) leads to a lack of disease detection efficiency. Among GLUTs, GLUT5 stands out as a prominent target for developing specific molecular tools due to its association with metabolic diseases, including cancer. This work reports a non-radiolabeled fluoride (
19 F) coumarin-based glycoconjugate of 2,5-anhydro-D-mannitol as a potential PET imaging probe that targets the GLUT5 transporter. Inherent fluorescent properties of the coumarin fluorophore allowed us to establish the probe's uptake efficiency and GLUT5-specificity in a GLUT5-positive breast cell line using fluorescence detection techniques. The click chemistry approach employed in the design of the probe enables late-stage functionalization, an essential requirement for obtaining the radiolabeled analog of the probe for future in vivo cancer imaging applications. The high affinity of the probe to GLUT5 allowed for the effective uptake in nutrition-rich media.- Published
- 2022
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8. Near-Infrared Fluorescent Probes with Amine-Incorporated Xanthene Platforms for the Detection of Hypoxia.
- Author
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Wan S, Vohs T, Steenwinkel TE, White WR, Lara-Ramirez A, Luck RL, Werner T, Tanasova M, and Liu H
- Abstract
Three fluorescent probes A , B , and C that function in the near-infrared wavelengths and utilize pseudo xanthene platforms with an oxygen atom at the 10-position replaced by a [Me-N]
2- group have been created to identify hypoxia via nitroreductase determinations at the 0.04, 0.10, and 0.19 ng/mL levels. Theoretical calculations suggest that the probes are not planar due to steric interactions. Absorptions of photons result in the transition of electron density from the indoline moieties to delocalized orbitals on the anthranilic section, ending up on the nitro groups of the electron-poor (i.e., nonreduced) probes (i.e., A , B , and C ), whereas those for the more electron-rich (i.e., reduced) probes consisted of movement from the indoline groups to the right side of the anthranilic sections, resulting in a shift in absorption.- Published
- 2022
- Full Text
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9. Importance of GLUT Transporters in Disease Diagnosis and Treatment.
- Author
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Ismail A and Tanasova M
- Subjects
- Animals, Biological Transport, Fructose, Glucose metabolism, Mammals metabolism, Glucose Transport Proteins, Facilitative genetics, Glucose Transport Proteins, Facilitative metabolism, Membrane Transport Proteins metabolism
- Abstract
Facilitative sugar transporters (GLUTs) are the primary method of sugar uptake in all mammalian cells. There are 14 different types of those transmembrane proteins, but they transport only a handful of substrates, mainly glucose and fructose. This overlap and redundancy contradict the natural tendency of cells to conserve energy and resources, and has led researchers to hypothesize that different GLUTs partake in more metabolic roles than just sugar transport into cells. Understanding those roles will lead to better therapeutics for a wide variety of diseases and disorders. In this review we highlight recent discoveries of the role GLUTs play in different diseases and disease treatments.
- Published
- 2022
- Full Text
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10. Targeting of GLUT5 for Transporter-Mediated Drug-Delivery Is Contingent upon Substrate Hydrophilicity.
- Author
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Nahrjou N, Ghosh A, and Tanasova M
- Subjects
- Antineoplastic Agents, Alkylating pharmacology, Breast drug effects, Breast metabolism, Breast Neoplasms drug therapy, Breast Neoplasms metabolism, Female, Humans, Hydrophobic and Hydrophilic Interactions, Mannitol metabolism, Substrate Specificity, Breast cytology, Breast Neoplasms pathology, Chlorambucil pharmacology, Glucose Transporter Type 5 metabolism, Mannitol analogs & derivatives
- Abstract
Specific link between high fructose uptake and cancer development and progression highlighted fructose transporters as potential means to achieve GLUT-mediated discrimination between normal and cancer cells. The gained expression of fructose-specific transporter GLUT5 in various cancers offers a possibility for developing cancer-specific imaging and bioactive agents. Herein, we explore the feasibility of delivering a bioactive agent through cancer-relevant fructose-specific transporter GLUT5. We employed specific targeting of GLUT5 by 2,5-anhydro-D-mannitol and investigated several drug conjugates for their ability to induce cancer-specific cytotoxicity. The proof-of-concept analysis was carried out for conjugates of chlorambucil (CLB) in GLUT5-positive breast cancer cells and normal breast cells. The cytotoxicity of conjugates was assessed over 24 h and 48 h, and significant dependence between cancer-selectivity and conjugate size was observed. The differences were found to relate to the loss of GLUT5-mediated uptake upon increased conjugate size and hydrophobicity. The findings provide information on the substrate tolerance of GLUT5 and highlight the importance of maintaining appropriate hydrophilicity for GLUT-mediated delivery.
- Published
- 2021
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11. Ratiometric Near-Infrared Fluorescent Probes Based on Hemicyanine Dyes Bearing Dithioacetal and Formal Residues for pH Detection in Mitochondria.
- Author
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Yan Y, Zhang Y, Xia S, Wan S, Vohs T, Tanasova M, Luck RL, and Liu H
- Subjects
- Cell Death, Fluorescent Dyes chemical synthesis, HeLa Cells, Humans, Hydrogen-Ion Concentration, Optical Phenomena, Spectrometry, Fluorescence, Water chemistry, Carbocyanines chemistry, Fluorescent Dyes chemistry, Mitochondria metabolism
- Abstract
Ratiometric near-infrared fluorescent probes ( AH
+ and BH+ ) have been prepared for pH determination in mitochondria by attaching dithioacetal and formal residues onto a hemicyanine dye. The reactive formyl group on probe BH+ allows for retention inside mitochondria as it can react with a protein primary amine residue to form an imine under slightly basic pH 8.0. Probes AH+ and BH+ display ratiometric fluorescent responses to pH changes through the protonation and deprotonaton of a hydroxy group in hemicyanine dyes with experimentally determined p K a values of 6.85 and 6.49, respectively. Calculated p Ka values from a variety of theoretical methods indicated that the SMDBONDI method of accounting for solvent and van der Waals radii plus including a water molecule located near the site of protonation produced the closest overall agreement with the experimental values at 7.33 and 6.14 for AH+ and BH+ respectively.- Published
- 2021
- Full Text
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12. Fluorescent probes with high pKa values based on traditional, near-infrared rhodamine, and hemicyanine fluorophores for sensitive detection of lysosomal pH variations.
- Author
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Mazi W, Adhikari R, Zhang Y, Xia S, Fang M, Luck RL, Tajiri M, Tiwari A, Tanasova M, and Liu H
- Subjects
- Boronic Acids chemistry, Cell Line, Tumor, Esters chemistry, Fluorescence, HeLa Cells, Human Umbilical Vein Endothelial Cells, Humans, Hydrogen-Ion Concentration, Molecular Probes chemistry, Spironolactone chemistry, Xanthenes, Carbocyanines chemistry, Fluorescent Dyes chemistry, Lysosomes chemistry, Rhodamines chemistry, Spectroscopy, Near-Infrared
- Abstract
Sterically hindered fluorescent probes (A-C) have been developed by introducing 2-aminophenylboronic acid pinacol ester to a traditional, A, a near-infrared rhodamine dye, B, and a near-infrared hemicyanine dye, C, forming closed spirolactam ring structures. Probe A was non-fluorescent under basic pH conditions whereas probes B and C were moderately fluorescent with fluorescence quantum yields of 9% and 5% in pH 7.4 PBS buffer containing 1% ethanol, respectively. With all probes increasing acidity leads to significant increases in fluorescence at 580 nm, 644 and 744 nm for probes A, B and C with fluorescence quantum yields of 26%, 21% and 10% in pH 4.5 PBS buffer containing 1% ethanol, respectively. Probes A, B and C were calculated to have pK
a values of 5.81, 5.45 and 6.97. The difference in fluorescence under basic conditions is ascribed to easier opening of the closed spirolactam ring configurations due to significant steric hindrance between the 2-aminophenylboronic acid pinacol ester residue and an adjacent H atom in the xanthene derivative moiety in probe B or C. The probes show fast, reversible, selective and sensitive fluorescence responses to pH changes, and are capable of sensing lysosomal pH variations in living cells., (Copyright © 2019 Elsevier Inc. All rights reserved.)- Published
- 2019
- Full Text
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13. Electrophilic oligodeoxynucleotide synthesis using dM-Dmoc for amino protection.
- Author
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Shahsavari S, Eriyagama DNAM, Halami B, Begoyan V, Tanasova M, Chen J, and Fang S
- Abstract
Solid-phase synthesis of electrophilic oligodeoxynucleotides (ODNs) was achieved using dimethyl-Dmoc (dM-Dmoc) as amino protecting group. Due to the high steric hindrance of the 2-(propan-2-ylidene)-1,3-dithiane side product from deprotection, the use of excess nucleophilic scavengers such as aniline to prevent Michael addition of the side product to the deprotected ODN during ODN cleavage and deprotection was no longer needed. The improved technology was demonstrated by the synthesis and characterization of five ODNs including three modified ones. The modified ODNs contained the electrophilic groups ethyl ester, α-chloroamide, and thioester. Using the technology, the sensitive groups can be installed at any location within the ODN sequences without using any sequence- or functionality-specific conditions and procedures.
- Published
- 2019
- Full Text
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14. Detecting Zn(II) Ions in Live Cells with Near-Infrared Fluorescent Probes.
- Author
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Fang M, Xia S, Bi J, Wigstrom TP, Valenzano L, Wang J, Tanasova M, Luck RL, and Liu H
- Subjects
- HeLa Cells, Humans, Microscopy, Fluorescence, Amines chemistry, Amines pharmacology, Carbocyanines chemistry, Carbocyanines pharmacology, Fluorescent Dyes chemistry, Fluorescent Dyes pharmacology, Picolinic Acids chemistry, Picolinic Acids pharmacology, Zinc metabolism
- Abstract
Two near-infrared fluorescent probes ( A and B ) containing hemicyanine structures appended to dipicolylamine (DPA), and a dipicolylamine derivative where one pyridine was substituted with pyrazine, respectively, were synthesized and tested for the identification of Zn(II) ions in live cells. In both probes, an acetyl group is attached to the phenolic oxygen atom of the hemicyanine platform to decrease the probe fluorescence background. Probe A displays sensitive fluorescence responses and binds preferentially to Zn(II) ions over other metal ions such as Cd
2+ ions with a low detection limit of 0.45 nM. In contrast, the emission spectra of probe B is not significantly affected if Zn(II) ions are added. Probe A possesses excellent membrane permeability and low cytotoxicity, allowing for sensitive imaging of both exogenously supplemented Zn(II) ions in live cells, and endogenously releases Zn(II) ions in cells after treatment of 2,2-dithiodipyridine., Competing Interests: The authors declare no conflict of interest.- Published
- 2019
- Full Text
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15. Fructose and prostate cancer: toward an integrated view of cancer cell metabolism.
- Author
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Carreño D, Corro N, Torres-Estay V, Véliz LP, Jaimovich R, Cisternas P, San Francisco IF, Sotomayor PC, Tanasova M, Inestrosa NC, and Godoy AS
- Subjects
- Animals, Biological Transport, Biomarkers, Energy Metabolism, Gene Expression, Humans, Male, Monosaccharide Transport Proteins genetics, Monosaccharide Transport Proteins metabolism, Prostatic Neoplasms diagnosis, Prostatic Neoplasms genetics, Prostatic Neoplasms therapy, Carbohydrate Metabolism, Fructose metabolism, Prostatic Neoplasms metabolism
- Abstract
Activation of glucose transporter-1 (Glut-1) gene expression is a molecular feature of cancer cells that increases glucose uptake and metabolism. Increased glucose uptake is the basis for the clinical localization of primary tumors using positron emission tomography (PET) and 2-deoxy-2-[18F]-fluoro-D-glucose (FDG) as a radiotracer. However, previous studies have demonstrated that a considerable number of cancers, which include prostate cancer (CaP), express low to undetectable levels of Glut-1 and that FDG-PET has limited clinical applicability in CaP. This observation could be explained by a low metabolic activity of CaP cells that may be overcome using different hexoses, such as fructose, as the preferred energy source. However, these hypotheses have not been examined critically in CaP. This review article summarizes what is currently known about transport and metabolism of hexoses, and more specifically fructose, in CaP and provides experimental evidences indicating that CaP cells may have increased capacity to transport and metabolize fructose in vitro and in vivo. Moreover, this review highlights recent findings that allow better understanding of how metabolism of fructose may regulate cancer cell proliferation and how fructose uptake and metabolism, through the de novo lipogenesis pathway, may provide new opportunities for CaP early diagnosis, staging, and treatment.
- Published
- 2019
- Full Text
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16. Integrating molecular probes and molecular dynamics to reveal binding modes of GLUT5 activatory and inhibitory ligands.
- Author
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Ainsley J, Chaturvedi SS, Karabencheva-Christova TG, Tanasova M, and Christov CZ
- Abstract
Fructose transporter GLUT5 is characterized by unusual substrate specificity and is linked to a variety of metabolic disorders. A series of high-affinity GLUT5-specific sugar-based probes - ManCous - have been very recently described and efficiently used as reporters of GLUT5 activity in cells. Here we present several 1 microsecond molecular dynamics (MD) simulations of GLUT5 and its complexes with fructose and two different ManCou probes, in a solvated cell membrane environment. These simulations show key molecular interactions within GLUT5 that promote the passage of the substrate through vs. blockage of the transport mechanism. Identification of these specific interactions and their long-range effects on GLUT5 structure and dynamics provides an essential basis for the future development of GLUT5-specific inhibitors.
- Published
- 2018
- Full Text
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17. Fluorescent Probes Based on π-Conjugation Modulation between Hemicyanine and Coumarin Moieties for Ratiometric Detection of pH Changes in Live Cells with Visible and Near-infrared Channels.
- Author
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Xia S, Wang J, Bi J, Wang X, Fang M, Phillips T, May A, Conner N, Tanasova M, Luo FT, and Liu H
- Abstract
We report two ratiometric fluorescent probes based on π-conjugation modulation between coumarin and hemicyanine moieties for sensitive ratiometric detection of pH alterations in live cells by monitoring visible and near-infrared fluorescence changes. In a π-conjugation modulation strategy, a coumarin dye was conjugated to a near-infrared hemicyanine dye via a vinyl connection while lysosome-targeting morpholine ligand and o-phenylenediamine residue were introduced to the hemicyanine dye to form closed spirolactam ring structures in probes A and B , respectively. The probes show only visible fluorescence of the coumarin moiety under physiological and basic conditions because the hemicyanine moieties retain their closed spirolactam ring structures. However, decrease of pH to acidic condition causes spirolactam ring opening, and significantly enhances π-conjugation within the probes, thus generating new near-infrared fluorescence peaks of the hemicyanine at 755 nm and 740 nm for probes A and B , respectively. Moreover, the probes display ratiometric fluorescence response to pH with decreases of the coumarin fluorescence and increases of the hemicyanine fluorescence when pH changes from 7.4 to 2.5. The probes are fully capable of imaging pH changes in live cells with good ratiometric responses in visible and near-infrared channels, and effectively avoid fluorescence blind spots under neutral and basic pH conditions - an issue that typical intensity-based pH fluorescent probes run into. The probe design platform reported herein can be easily applied to prepare a variety of ratiometric fluorescent probes for detection of biological thiols, metal ions, reactive oxygen and nitrogen species by introducing appropriate functional groups to hemicyanine moiety.
- Published
- 2018
- Full Text
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18. Metabolism-Driven High-Throughput Cancer Identification with GLUT5-Specific Molecular Probes.
- Author
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Kannan S, Begoyan VV, Fedie JR, Xia S, Weseliński ŁJ, Tanasova M, and Rao S
- Subjects
- Breast Neoplasms metabolism, Female, Humans, Biological Transport genetics, Breast Neoplasms genetics, Glucose Transporter Type 5 genetics, Molecular Probes genetics
- Abstract
Point-of-care applications rely on biomedical sensors to enable rapid detection with high sensitivity and selectivity. Despite advances in sensor development, there are challenges in cancer diagnostics. Detection of biomarkers, cell receptors, circulating tumor cells, gene identification, and fluorescent tagging are time-consuming due to the sample preparation and response time involved. Here, we present a novel approach to target the enhanced metabolism in breast cancers for rapid detection using fluorescent imaging. Fluorescent analogs of fructose target the fructose-specific transporter GLUT5 in breast cancers and have limited to no response from normal cells. These analogs demonstrate a marked difference in adenocarcinoma and premalignant cells leading to a novel detection approach. The vastly different uptake kinetics of the analogs yields two unique signatures for each cell type. We used normal breast cells MCF10A, adenocarcinoma cells MCF7, and premalignant cells MCF10AneoT, with hepatocellular carcinoma cells HepG2 as the negative control. Our data indicated that MCF10AneoT and MCF7 cells had an observable difference in response to only one of the analogs. The response, observed as fluorescence intensity, leads to a two-point assessment of the cells in any sample. Since the treatment time is 10 min, there is potential for use in rapid on-site high-throughput diagnostics., Competing Interests: The authors declare no conflict of interest.
- Published
- 2018
- Full Text
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19. A cyanine-based fluorescent cassette with aggregation-induced emission for sensitive detection of pH changes in live cells.
- Author
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Fang M, Xia S, Bi J, Wigstrom TP, Valenzano L, Wang J, Mazi W, Tanasova M, Luo FT, and Liu H
- Subjects
- Carbocyanines chemical synthesis, Cell Survival, Energy Transfer, Ethylenes chemistry, Fluorescent Dyes chemical synthesis, HeLa Cells, Humans, Hydrogen-Ion Concentration, Molecular Structure, Quantum Theory, Spectrometry, Fluorescence, Carbocyanines chemistry, Fluorescent Dyes chemistry
- Abstract
An aggregation-induced emission (AIE) cyanine-based fluorescent cassette with a large pseudo-Stokes shift was designed and prepared to sensitively image pH changes in live cells via through-bond energy transfer (TBET) from a tetraphenylethene (TPE) donor to a cyanine acceptor.
- Published
- 2018
- Full Text
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20. Targeting Sugar Uptake and Metabolism for Cancer Identification and Therapy: An Overview.
- Author
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Tanasova M, Begoyan VV, and Weselinski LJ
- Subjects
- Antineoplastic Agents chemistry, Biological Transport drug effects, Humans, Neoplasms diagnosis, Antineoplastic Agents pharmacology, Neoplasms drug therapy, Neoplasms metabolism, Sugars metabolism
- Abstract
Metabolic deregulations have emerged as a cancer characteristic, opening a broad avenue for strategies and tools to target cancer through sugar uptake and metabolism. High expression levels of sugar transporters in cancer cells offered glycoconjugation as an approach to achieve enhanced cellular accumulation of drugs and imaging agents, with the sugar moiety anchoring the bioactive cargo to cancer cells. On the other hand, high demand for sugar nutrients in cancers provided a new avenue to target cancer cells with metabolic or sugar uptake inhibitors to induce cancer cells starvation or death. This overview summarizes recent advances in targeting cancer cells through sugar transport for cancer detection and therapy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)
- Published
- 2018
- Full Text
- View/download PDF
21. Near-Infrared Fluorescent Probe for Sensitive Detection of Pb(II) Ions in Living Cells.
- Author
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Bi J, Fang M, Wang J, Xia S, Zhang Y, Zhang J, Vegesna G, Zhang S, Tanasova M, Luo FT, and Liu H
- Abstract
A new near-infrared fluorescent probe (NIR-PbP) for sensitive detection of Pb(II) ions in solution and living cells has been rationally designed and synthesized. The NIR-PbP is inherently non-fluorescent and gains fluorescence in the presence Pb(II) ions. The ion detection is based on Pb(II)-induced unmasking the fluorophore through the opening of the spyrocycle, with more than 500-fold fluorescence for sub-micromolar Pb(II) concentration. The NIR-PbP has high sensitivity, good photo-stability, low detection limit, and reversible response to Pb(II) ions.
- Published
- 2017
- Full Text
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22. Tuning Cross-Coupling Approaches to C3 Modification of 3-Deazapurines.
- Author
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Weseliński ŁJ, Begoyan V, Ferrier A, and Tanasova M
- Abstract
A general approach to C3 modification of purine scaffold through various types of cross-coupling reactions has been established. Tuning substrate electronics and reaction conditions resulted in the development of highly efficient sp
2 -sp, sp2 -sp2 , and sp2 -sp3 cross-coupling conditions for modification of 3-deazaadenine to access C3-modified adenine and hypoxanthine scaffolds. The optimized methodologies to access the corresponding 3-deazaadenosine phosphoramidites for solid-phase DNA synthesis have been demonstrated., Competing Interests: The authors declare no competing financial interest.- Published
- 2017
- Full Text
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23. Molecular Tools for Facilitative Carbohydrate Transporters (Gluts).
- Author
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Tanasova M and Fedie JR
- Subjects
- Amides chemical synthesis, Amides chemistry, Amides metabolism, Binding Sites, Biological Products chemistry, Biological Products metabolism, Glucose Transport Proteins, Facilitative antagonists & inhibitors, Glucose Transport Proteins, Facilitative genetics, Humans, Inhibitory Concentration 50, Neoplasms metabolism, Neoplasms pathology, Protein Binding, Glucose metabolism, Glucose Transport Proteins, Facilitative metabolism
- Abstract
Facilitative carbohydrate transporters-Gluts-have received wide attention over decades due to their essential role in nutrient uptake and links with various metabolic disorders, including diabetes, obesity, and cancer. Endeavors directed towards understanding the mechanisms of Glut-mediated nutrient uptake have resulted in a multidisciplinary research field spanning protein chemistry, chemical biology, organic synthesis, crystallography, and biomolecular modeling. Gluts became attractive targets for cancer research and medicinal chemistry, leading to the development of new approaches to cancer diagnostics and providing avenues for cancer-targeting therapeutics. In this review, the current state of knowledge of the molecular interactions behind Glut-mediated sugar uptake, Glut-targeting probes, therapeutics, and inhibitors are discussed., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2017
- Full Text
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24. Modulation of Cytotoxicity by Transcription-Coupled Nucleotide Excision Repair Is Independent of the Requirement for Bioactivation of Acylfulvene.
- Author
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Otto C, Spivak G, Aloisi CM, Menigatti M, Naegeli H, Hanawalt PC, Tanasova M, and Sturla SJ
- Subjects
- Activation, Metabolic, Cell Line, Humans, Sesquiterpenes pharmacokinetics, Spiro Compounds pharmacokinetics, DNA Repair, Sesquiterpenes pharmacology, Spiro Compounds pharmacology, Transcription, Genetic drug effects
- Abstract
Bioactivation as well as DNA repair affects the susceptibility of cancer cells to the action of DNA-alkylating chemotherapeutic drugs. However, information is limited with regard to the relative contributions of these processes to the biological outcome of metabolically activated DNA alkylating agents. We evaluated the influence of cellular bioactivation capacity and DNA repair on cytotoxicity of the DNA alkylating agent acylfulvene (AF). We compared the cytotoxicity and RNA synthesis inhibition by AF and its synthetic activated analogue iso-M0 in a panel of fibroblast cell lines with deficiencies in transcription-coupled (TC-NER) or global genome nucleotide excision repair (GG-NER). We related these data to the inherent bioactivation capacity of each cell type on the basis of mRNA levels. We demonstrated that specific inactivation of TC-NER by siRNA had the largest positive impact on AF activity in a cancer cell line. These findings establish that transcription-coupled DNA repair reduces cellular sensitivity to AF, independent of the requirement for bioactivation.
- Published
- 2017
- Full Text
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25. Altered minor-groove hydrogen bonds in DNA block transcription elongation by T7 RNA polymerase.
- Author
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Tanasova M, Goeldi S, Meyer F, Hanawalt PC, Spivak G, and Sturla SJ
- Subjects
- Base Pairing, Base Sequence, Hydrogen Bonding, Models, Molecular, RNA chemistry, RNA genetics, RNA Stability, DNA chemistry, DNA genetics, DNA-Directed RNA Polymerases metabolism, Transcription Elongation, Genetic, Viral Proteins metabolism
- Abstract
DNA transcription depends upon the highly efficient and selective function of RNA polymerases (RNAPs). Modifications in the template DNA can impact the progression of RNA synthesis, and a number of DNA adducts, as well as abasic sites, arrest or stall transcription. Nonetheless, data are needed to understand why certain modifications to the structure of DNA bases stall RNA polymerases while others are efficiently bypassed. In this study, we evaluate the impact that alterations in dNTP/rNTP base-pair geometry have on transcription. T7 RNA polymerase was used to study transcription over modified purines and pyrimidines with altered H-bonding capacities. The results suggest that introducing wobble base-pairs into the DNA:RNA heteroduplex interferes with transcriptional elongation and stalls RNA polymerase. However, transcriptional stalling is not observed if mismatched base-pairs do not H-bond. Together, these studies show that RNAP is able to discriminate mismatches resulting in wobble base-pairs, and suggest that, in cases of modifications with minor steric impact, DNA:RNA heteroduplex geometry could serve as a controlling factor for initiating transcription-coupled DNA repair., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2015
- Full Text
- View/download PDF
26. Sensing remote chirality: stereochemical determination of β-, γ-, and δ-chiral carboxylic acids.
- Author
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Tanasova M, Anyika M, and Borhan B
- Subjects
- Models, Molecular, Stereoisomerism, Carboxylic Acids chemistry
- Abstract
Determining the absolute stereochemisty of small molecules bearing remote nonfunctionalizable stereocenters is a challenging task. Presented is a solution in which appropriately substituted bis(porphyrin) tweezers are used. Complexation of a suitably derivatized β-, γ-, or δ-chiral carboxylic acid to the tweezer induces a predictable helicity of the bis(porphyrin), which is detected as a bisignate Cotton Effect (ECCD). The sign of the ECCD curve is correlated with the absolute stereochemistry of the substrate based on the derived working mnemonics in a predictable manner., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2015
- Full Text
- View/download PDF
27. Fluorescent THF-based fructose analogue exhibits fructose-dependent uptake.
- Author
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Tanasova M, Plutschack M, Muroski ME, Sturla SJ, Strouse GF, and McQuade DT
- Subjects
- Biological Transport, Fluorescent Dyes chemistry, Fructose chemistry, Glucose Transporter Type 5 metabolism, Humans, MCF-7 Cells, Mannitol analogs & derivatives, Mannitol pharmacokinetics, Microscopy, Confocal, Fluorescent Dyes pharmacokinetics, Fructose analogs & derivatives, Fructose pharmacokinetics
- Abstract
Recent publications suggest that high dietary fructose might play a significant role in cancer metabolism and can exacerbate a number of aspects of metabolic syndrome. Addressing the role that fructose plays in human health is a controversial question and requires a detailed understanding of many factors including the mechanism of fructose transport into healthy and diseased cells. Fructose transport into cells is thought to be largely mediated by the passive hexose transporters Glut2 and Glut5. To date, no probes that can be selectively transported by one of these enzymes but not by the other have been identified. The data presented here indicate that, in MCF-7 cells, a 1-amino-2,5-anhydro-D-mannitol-based fluorescent NBDM probe is transported twice as efficiently as fructose and that this takes place with the aid of Glut5. Its Glut5 specificity and differential uptake in cancer cells and in normal cells suggest this NBDM probe as a potentially useful tool for cross-cell-line correlation of Glut5 transport activity., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2013
- Full Text
- View/download PDF
28. Chemistry and biology of acylfulvenes: sesquiterpene-derived antitumor agents.
- Author
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Tanasova M and Sturla SJ
- Subjects
- Alkylating Agents chemistry, Alkylating Agents pharmacology, Animals, Antineoplastic Agents pharmacokinetics, Aziridines chemistry, Clinical Trials as Topic, Cyclopropanes chemistry, DNA Damage drug effects, Enzyme Inhibitors chemistry, Enzyme Inhibitors pharmacology, Glutathione Reductase antagonists & inhibitors, Humans, Mice, Sesquiterpenes pharmacology, Tissue Distribution, Xenograft Model Antitumor Assays, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Sesquiterpenes chemistry, Spiro Compounds chemistry, Spiro Compounds pharmacology
- Published
- 2012
- Full Text
- View/download PDF
29. Enhancement of exciton coupled circular dichroism with sterically encumbered bis-porphyrin tweezers.
- Author
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Tanasova M, Vasileiou C, Olumolade OO, and Borhan B
- Abstract
Porphyrin tweezers have been successfully used as hosts for the absolute stereochemical determination of a variety of chiral compounds. A set of new porphyrin tweezers with substituted aryl groups on the meso position of the porphyrin rings have been synthesized. The modified tweezers are used as hosts for the stereochemical determination of chiral diamines and carrier-derivatized alpha-chiral carboxylic acids in order to monitor the influence of the various substitutions of the aryl group on the amplitude and sign of the ECCD couplet. t-Butyl substitution at the meta positions of the porphyrin's meso phenyl substituents leads to enhanced ECCD amplitudes., ((c) 2008 Wiley-Liss, Inc.)
- Published
- 2009
- Full Text
- View/download PDF
30. Ionic reagent for controlling the gas-phase fragmentation reactions of cross-linked peptides.
- Author
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Lu Y, Tanasova M, Borhan B, and Reid GE
- Subjects
- Cross-Linking Reagents chemical synthesis, Peptides chemistry, Succinimides chemical synthesis, Tandem Mass Spectrometry methods, Cross-Linking Reagents chemistry, Ions chemistry, Peptides analysis, Spectrometry, Mass, Electrospray Ionization methods, Succinimides chemistry
- Abstract
Chemical cross-linking combined with proteolytic digestion and mass spectrometry (MS) is a promising approach to provide inter- and intramolecular distance constraints for the structural characterization of protein topologies and functional multiprotein complexes. Despite the relative straightforwardness of these methodologies, the identification and characterization of cross-linked proteins presents a significant analytical challenge, due to the complexity of the resultant peptide mixtures, as well as the array of inter-, intra-, or "dead-end"-cross-linked peptides that may be generated from a single cross-linking experiment. To address these issues, we describe here the synthesis, characterization, and initial evaluation of a novel "fixed charge" sulfonium ion-containing crosslinking reagent, S-methyl 5,5'-thiodipentanoylhydroxysuc-cinimide. The peptide products obtained by reaction with this reagent are all shown to fragment exclusively via facile cleavage of the C-S bond directly adjacent to the fixed charge during CID-MS/MS, resulting in the formation of characteristic product ions that enable the presence and type (i.e., inter, intra, or dead-end) of the cross-linked products to be readily determined, independently of the "proton mobility" of the precursor ion. Subsequent isolation and dissociation of these products by MS3 provides additional structural information required for identification of the peptide sequences involved in the cross-linking reactions, as well as for characterization of the specific site(s) at which cross-linking has occurred. The specificity of these gas-phase fragmentation reactions, as well as the solubility and stability of the cross-linking reagent under aqueous conditions, suggests that this strategy holds great promise for use in future studies aimed at the structural analysis of large proteins or multiprotein assemblies.
- Published
- 2008
- Full Text
- View/download PDF
31. Fluorinated porphyrin tweezer: a powerful reporter of absolute configuration for erythro and threo diols, amino alcohols, and diamines.
- Author
-
Li X, Tanasova M, Vasileiou C, and Borhan B
- Subjects
- Binding, Competitive, Metalloporphyrins chemical synthesis, Models, Molecular, Molecular Structure, Static Electricity, Stereoisomerism, Alcohols chemistry, Amino Alcohols chemistry, Diamines chemistry, Metalloporphyrins chemistry
- Abstract
A general and sensitive nonempirical protocol to determine the absolute configurations of erythro and threo diols, amino alcohols, and diamines is reported. Binding of diols to the porphyrin tweezer system is greatly enhanced by increasing the Lewis acidity of the metalloporphyrin. Supramolecular complexes formed between the porphyrin tweezer host and chiral substrates exhibited exciton-coupled bisignate CD spectra with predictable signs based on the substituents on the chiral center. The working model suggests that the observed helicity of the porphyrin tweezer is dictated via steric differentiation experienced by the porphyrin ring bound to each chiral center. A variety of erythro and threo substrates were investigated to verify this chiroptical method. Their absolute configurations were unequivocally determined, and thus a general mnemonic is provided for the assignment of chirality.
- Published
- 2008
- Full Text
- View/download PDF
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