A5087883720- Advanced biosensing and bioanalysis techniques
- DNA and Nucleic Acid Chemistry
- RNA Interference and Gene Delivery
- Metal complexes synthesis and properties
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- RNA Research and Splicing
- Cancer-related molecular mechanisms research
- Click Chemistry and Applications
- DNA Repair Mechanisms
- HIV Research and Treatment
- Chemical Synthesis and Analysis
- Malaria Research and Control
- Lanthanide and Transition Metal Complexes
- Molecular Biology Techniques and Applications
- Crystallization and Solubility Studies
- HIV/AIDS drug development and treatment
- Esophageal Cancer Research and Treatment
- X-ray Diffraction in Crystallography
- Metal-Catalyzed Oxygenation Mechanisms
- Photochromic and Fluorescence Chemistry
- Ultrasound and Hyperthermia Applications
- Enzyme Structure and Function
- Cancer Research and Treatments
- Nanoparticle-Based Drug Delivery
Hebrew University of Jerusalem
2014-2024
Hadassah Medical Center
2020
State Institute for Drug Control
2014
Czech Academy of Sciences, Institute of Biophysics
2010
California Institute of Technology
2004-2007
University of Utah
2005
Weizmann Institute of Science
2001-2005
Pancreatic ductal adenocarcinoma (PDA) represents an unmet therapeutic challenge. PDA is addicted to the activity of mutated KRAS oncogene which considered so far undruggable target. We propose approach target effectively in patients using RNA interference. To meet this challenge, we have developed a local prolonged siRNA delivery system (Local Drug EluteR, LODER) shedding against (siG12D LODER). The siG12D LODER was assessed for its structural, release, and properties vitro vivo. effect on...
MutY and endonuclease III, two DNA glycosylases from Escherichia coli, AfUDG, a uracil glycosylase Archeoglobus fulgidus, are all base excision repair enzymes that contain the [4Fe-4S](2+) cofactor. Here we demonstrate that, when bound to DNA, these become redox-active; binding shifts redox potential of [4Fe-4S](3+/2+) couple range characteristic high-potential iron proteins activates toward oxidation. Electrochemistry on DNA-modified electrodes reveals potentials for Endo III AfUDG 58 95 mV...
Finding bacterial cellular targets for developing novel antibiotics has become a major challenge in fighting resistant pathogenic bacteria. We present compound, Relacin, designed to inhibit (p)ppGpp production by the ubiquitous enzyme RelA that triggers Stringent Response. Relacin inhibits vitro and reduces vivo. Moreover, affects entry into stationary phase Gram positive bacteria, leading dramatic reduction cell viability. When is added sporulating Bacillus subtilis cells, it strongly...
Significance How cells specifically express only a single gene among numerous equivalent copies within their genomes is one of the unsolved mysteries in field eukaryotic expression. The molecular mechanisms that underlie mutually exclusive expression are key for understanding virulence Plasmodium falciparum , parasite responsible deadliest form human malaria. P. expresses its primary determinants manner and evades immune attack through switches between different variants large family named...
Abstract Alternative splicing, a fundamental step in gene expression, is deregulated many diseases. Splicing factors (SFs), which regulate this process, are up- or down regulated mutated several diseases including cancer. To date, there no inhibitors that directly inhibit the activity of SFs. We designed decoy oligonucleotides, composed repeats RNA motif, recognized by single SF. Here we show oligonucleotides targeting splicing RBFOX1/2, SRSF1 and PTBP1, can specifically bind to their...
DNA charge transport (CT) chemistry provides a route to carry out oxidative damage from distance in reaction that is sensitive mismatches and lesions. Here, DNA-mediated CT also leads oxidation of DNA-bound base excision repair enzyme, MutY. Ru(III), generated through flash/quench technique, found promote the [4Fe-4S] 2+ cluster MutY 3+ its decomposition product [3Fe-4S] 1+ . Flash/quench experiments monitored by EPR spectroscopy reveal spectra with g = 2.08, 2.06, 2.02, characteristic...
Losing ligands rapidly: PtIV complexes with haloacetato can hydrolyze rapidly under biological conditions (pH 7 and 37 °C, see scheme) the rate increases increasing pH value. Possible mechanisms for this hydrolysis are examined using H218O ESI-MS analysis. As a service to our authors readers, journal provides supporting information supplied by authors. Such materials peer reviewed may be re-organized online delivery, but not copy-edited or typeset. Technical support issues arising from...
Detection of mRNA alterations is a promising approach for identifying biomarkers as means differentiating benign from malignant lesions. By choosing the KRAS oncogene target gene, two types molecular beacons (MBs) based on either phosphothioated DNA (PS-DNA-MB) or peptide nucleic acid (TO-PNA-MB, where TO = thiazole orange) were synthesized and compared in vitro vivo. Their specificity was examined wild-type (HT29) codon 12 point mutation (Panc-1, SW480) cells. Incubation both with total RNA...
The gene encoding the kinase Mnk2 (MKNK2) is alternatively spliced to produce two isoforms—Mnk2a and Mnk2b. We previously showed that Mnk2a downregulated in several types of cancer acts as a tumor suppressor by activation p38–MAPK stress pathway, inducing apoptosis. Moreover, overexpression suppressed Ras-induced transformation culture vivo. In contrast, Mnk2b isoform pro-oncogenic factor. this study, we designed modified-RNA antisense oligonucleotides screened for those specifically induce...
The evolution of drug resistance to many antimalarial drugs in the lethal strain malaria (Plasmodium falciparum) has been a great concern over past 50 years. Among these drugs, artemisinin become less effective for treating malaria. Indeed, several P. falciparum variants have resistant this drug, as elucidated by specific mutations pfK13 gene. This study presents development diagnostic kit detection common point mutation gene falciparum, namely, C580Y mutation. FIT-PNAs (forced-intercalation...
The electrochemistry of DNA films modified with different redox probes linked to through saturated and conjugated tethers was investigated. Experiments feature two bound on surfaces: anthraquinone (AQ)-modified uridines incorporated into thiolated gold (Au) 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO)-modified in pyrene-labeled highly oriented pyrolytic graphite (HOPG). these labels when has been examined containing both well matched mismatched DNA. DNA-mediated is found be effective for the...
In Plasmodium falciparum, the deadliest form of human malaria, nuclear periphery has drawn much attention due to its role as a sub-nuclear compartment involved in virulence gene expression. Recent data have implicated components envelope regulating expression several eukaryotes. Special been given nucleoporins that compose pore complex. However, very little is known about parasites. Here we characterize PfSec13, an unusual nucleoporin P. which shows unique structural similarities suggesting...
Abstract The design of Pt IV pro‐drugs as anticancer agents is predicated on the assumption that they will not undergo substitution reactions before entering cancer cell. Attempts to improve cytotoxic properties included use haloacetato axial ligands. Herein, we demonstrate complexes with trifluoroacetato (TFA) or dichloroacetato (DCA) ligands can be unstable under biologically relevant conditions and readily hydrolysis, which results in loss TFA DCA half‐lives for two at pH 7 37 °C range...
Peptide nucleic acid bis-quinoline conjugates are reported as attractive far-red emitting probes that detect mutated mRNA in living cells at SNP resolution.
Osteosarcoma (OS) is an aggressive malignancy affecting mostly children and adolescents. MicroRNAs (miRNAs) play important roles in OS development progression. Here we found that miR-16-1-3p miR-16-2-3p "passenger" strands, as well the "lead" miR-16-5p strand, are frequently downregulated possess strong tumor suppressive functions human OS. Furthermore, report different although strongly overlapping for cells. Ectopic expression of these miRNAs affected primary growth, metastasis seeding...
Despite a low copy number within the cell, base excision repair (BER) enzymes readily detect DNA lesions and mismatches. These also contain [Fe4S4] clusters, yet redox role for these iron cofactors had been unclear. Here, we provide evidence that BER proteins may use DNA-mediated chemistry as part of signaling mechanism to lesions. By using chemically modified bases, show electron trapping on in solution with bound by paramagnetic resonance (EPR) spectroscopy. We demonstrate transfer from...
A variety of diseases are related to mitochondrial dysfunction. Hence, the ability transport drugs mitochondria that otherwise cell impermeable would be great therapeutic potential. Triphenylphosphonium (TPP) cations have been shown accumulate in when attached small molecules. Here we report on consequence increasing number TPP moieties covalently linked a model hydrophilic peptide Hemagglutinin (HA). By extending HA with l-lysine amino acids which TPP's through ε-amine, systematically...
One of the major concerns in treating malaria by conventional small drug molecules is rapid emergence resistance. Specific silencing essential genes antisense oliogomers has been proposed as an alternative approach that may result antimalarial activity which not associated with In addition, such could be important biological tool for studying many genes' function reverse genetics. Here we present a novel methodology using peptide nucleic acids (PNAs) useful gene Plasmodium falciparum. PNAs,...
Efficient delivery of nucleic acids into cells still remains a great challenge. Peptide (PNAs) are DNA analogues with neutral backbone and synthesized by solid phase peptide chemistry. This allows straightforward synthetic route to introduce linear short (a.k.a. cell-penetrating peptide) the PNA molecule as means facilitating cellular uptake PNAs. Herein, we have devised in which cyclic is prepared on support extended molecule, where all syntheses accomplished phase. conjugation need only...