A5076498595- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- RNA modifications and cancer
- RNA Interference and Gene Delivery
- Biochemical and Molecular Research
- PI3K/AKT/mTOR signaling in cancer
- Click Chemistry and Applications
- Monoclonal and Polyclonal Antibodies Research
- Growth Hormone and Insulin-like Growth Factors
- Chemical Synthesis and Analysis
- RNA regulation and disease
- DNA and Nucleic Acid Chemistry
- Viral Infections and Immunology Research
- Trypanosoma species research and implications
- Polyamine Metabolism and Applications
- Molecular Biology Techniques and Applications
- Genetic and phenotypic traits in livestock
- Adenosine and Purinergic Signaling
- CRISPR and Genetic Engineering
- Digestive system and related health
- Advanced biosensing and bioanalysis techniques
- Ferrocene Chemistry and Applications
- Nuclear Structure and Function
- Genetically Modified Organisms Research
- Asthma and respiratory diseases
University of Warsaw
2014-2024
Institute of Experimental Physics of the Slovak Academy of Sciences
2014-2016
Institute of Biochemistry and Biophysics, Polish Academy of Sciences
2002
Warsaw University of Life Sciences
1999
Along with a growing interest in mRNA-based gene therapies, efforts are increasingly focused on reaching the full translational potential of mRNA, as major obstacle for vivo applications is sufficient expression exogenously delivered mRNA. One method to overcome this limitation chemically modifying 7-methylguanosine cap at 5' end mRNA (m7Gppp-RNA). We report novel class analogs designed reagents modification. The carry 1,2-dithiodiphosphate moiety various positions along tri- or...
Modified mRNA cap analogs aid in the study of mRNA-related processes and may enable creation novel therapeutic interventions. We report synthesis properties 11 dinucleotide bearing a single boranophosphate modification at either α-, β- or γ-position 5′,5′-triphosphate chain. The compounds can potentially serve as inhibitors translation cancer cells reagents for increasing expression proteins vivo from exogenous mRNAs. BH3-analogs were tested substrates binding partners two major cytoplasmic...
An effective and facile synthesis of six novel tetraphosphate cap analogs modified with a methylenebis(phosphonate) moiety (1–6) is presented. Analogs have been rationally designed to bind tightly the eukaryotic initiation factor 4E (eIF4E) responsible for binding during translation, increased stability owing resistance enzymatic degradation. Final compounds turned out significantly higher association constant values (KAS) eIF4E (5–9 fold than standard). Four were resistant towards...
Decapping is an essential step in multiple pathways of mRNA degradation. Previously, we synthesized mRNAs containing caps that were resistant to decapping, both dissect the various for degradation and stabilize more sustained protein expression. α-β CH 2 group are vitro cleavage by decapping enzyme hDcp2 but poorly translated. S substitution at β-phosphate well translated only partially hDcp2. We now describe seven new cap analogs substituted with BH 3 or Se, either β-γ O NH. The differ...
Analogues of the mRNA 5'-cap are useful tools for studying translation and degradation, with emerging potential applications in novel therapeutic interventions including gene therapy. We report synthesis mono- dinucleotide cap analogues containing dihalogenmethylenebisphosphonate moiety (i.e. one bridging O atom substituted CCl2 or CF2) their properties context cellular translational decapping machineries, compared to phosphate-unmodified previously reported CH2-substituted caps. The were...
mRNA-based vaccines are relatively new technologies that have been in the field of interest research centers and pharmaceutical companies recent years. Such therapeutics an attractive alternative for DNA-based since they provide material can be used with no risk genomic integration. Additionally, mRNA quite easily engineered to introduce modifications different applications or modulate its properties, example, increase translational efficiency stability, which is not available DNA vectors....
In the fight against cancer, researchers have turned their attention to eukaryotic initiation factor eIF4E, a protein whose increased level is strongly correlated with development and progression of various types cancer. Among numerous strategies devised tackle eIF4E overexpression, use 5′ end mRNA cap analogues has emerged as promising approach. Here, we present new candidates potent m7GMP for inhibiting translation interfacing eIF4E. By employing an appropriate strategy, synthesized doubly...
Active partitioning of low-copy number plasmids requires two proteins belonging to the ParA and ParB families a cis-acting site which acts upon. separation clusters plasmid molecules defined locations in cell before division ensures stable inheritance plasmids. The central control operon IncP-1 codes for regulatory involved global transcriptional operons vegetative replication, maintenance conjugative transfer. Two these proteins, IncC KorB, also play role active partitioning, as homologues,...
We describe the chemical synthesis and preliminary biophysical biochemical characterization of a series mRNA 5′-end (cap) analogs designed as reagents for obtaining molecules with augmented translation efficiency stability in vivo useful tools to study metabolism. The share three structural features: (i) 5′,5′-bridge is elongated tetraphosphate increase their affinity initiation factor eIF4E; (ii) single phosphorothioate modification at either α, β, γ or δ-position has been made decrease...
Decapping scavenger (DcpS) enzymes catalyze the cleavage of a residual cap structure following 3' → 5' mRNA decay. Some previous studies suggested that both m(7)GpppG and m(7)GDP were substrates for DcpS hydrolysis. Herein, we show mononucleoside diphosphates, (7-methylguanosine diphosphate) m(3)(2,2,7)GDP (2,2,7-trimethylguanosine diphosphate), resulting from decapping by Dcp1/2 complex in decay, are not degraded recombinant proteins (human, nematode, yeast). Furthermore, whereas...
Proteins that have a histidine triad in their active sites belong to the HIT-protein superfamily. They are ubiquitous, involved metabolism of different nucleotides and catalyze hydrolysis and/or phosphorolysis liberating either corresponding 5′-NMP or 5′-NDP, respectively. We studied substrate specificity nine recombinant HIT-proteins with adenosine 5′-phosphosulfate (1), 5′-phosphoramidate (2), 5′-phosphorothioate (3), 5′-phosphorofluoride (4), diadenosine 5′,5′′′-P1,P3-triphosphate (5),...
We describe the synthesis and properties of five dinucleotide fluorescent cap analogues labelled at ribose 7-methylguanosine moiety with either anthraniloyl (Ant) or N-methylanthraniloyl (Mant), which have been designed for preparation mRNAs via transcription in vitro. Two bear a methylene modification triphosphate bridge, providing resistance against Dcp2 DcpS decapping enzymes. All these compounds were prepared by ZnCl2-mediated coupling nucleotide P-imidazolide fluorescently...
mRNA is a template for protein biosynthesis, and consequently transport, translation, turnover are key elements in the overall regulation of gene expression. Along with growing interest mechanisms regulating decay localization, there an increasing need tools enabling convenient fluorescent labeling or affinity tagging mRNA. We report new 5' cap analog-based that enable site-specific RNA within using N-hydroxysuccinimide (NHS) chemistry. explored two complementary methods: co-transcriptional...
Analogues of the eukaryotic messenger RNA 5′ end (m7G cap) are useful tools for studying mRNA fate and serve as reagents in vitro preparation capped mRNAs. We designed a biotin-labeled dinucleotide cap analogue that can be incorporated into transcripts to produce 5′-capped biotinylated mRNAs which retain their biological functionality may employed biotin–(strept)avidin technologies.
Synthetic analogs of the 5′ end mRNA (cap structure) are widely used in molecular studies on mechanisms cellular processes such as translation, intracellular transport, splicing, and turnover. The best-characterized cap binding protein is translation initiation factor 4E (eIF4E). Recognition by eIF4E a critical, rate-limiting step for efficient considered major target anticancer therapy. Here, we report facile methodology preparation N2-triazole-containing monophosphate present their...
Novel photo-crosslinking reagents for the analysis of biomolecules binding mRNA 5′ end.
Human Nudt16 (hNudt16) is a member of the Nudix family hydrolases, comprising enzymes catabolizing various substrates including canonical (d)NTPs, oxidized nonnucleoside polyphosphates, and capped mRNAs. Decapping activity Xenopus laevis (X29) homolog was observed in nucleolus, with high specificity toward U8 snoRNA. Subsequent studies have reported cytoplasmic localization mammalian cap hydrolysis initiating RNA turnover, similar to Dcp2. The present study focuses on hNudt16 its hydrolytic...
Beginning from the end (5′ end): Analogues of messenger RNA 5′ (cap) bearing an oxygen-to-selenium substitution at β position triphosphate bridge, which could be useful for X-ray crystallography, were synthesised. They also incorporated into transcripts to demonstrate that such a small change mRNA can improve properties whole molecule, example, its translation efficiency. Detailed facts importance specialist readers are published as "Supporting Information". Such documents peer-reviewed, but...
Decapping scavenger (DcpS) assists in precluding inhibition of cap-binding proteins by hydrolyzing cap species remaining after mRNA 3′→5′ degradation. Its significance was reported splicing, translation initiation and microRNA turnover. Here we examine the structure binding mode DcpS from Caenorhabditis elegans (CeDcpS) using a large collection chemically modified methylenebis(phosphonate), imidodiphosphate phosphorothioate analogs. We determine that CeDcpS is homodimer propose high accuracy...