A5068037314- RNA and protein synthesis mechanisms
- RNA Interference and Gene Delivery
- RNA Research and Splicing
- Chemical Synthesis and Analysis
- Click Chemistry and Applications
- Biochemical and Molecular Research
- Viral Infections and Immunology Research
- Advanced biosensing and bioanalysis techniques
- PI3K/AKT/mTOR signaling in cancer
- Mitochondrial Function and Pathology
- RNA modifications and cancer
- DNA and Nucleic Acid Chemistry
- Alzheimer's disease research and treatments
- Polyamine Metabolism and Applications
- RNA regulation and disease
- Sulfur-Based Synthesis Techniques
- Monoclonal and Polyclonal Antibodies Research
- Nuclear Structure and Function
- Lipid Membrane Structure and Behavior
- Biochemical Acid Research Studies
- HIV/AIDS drug development and treatment
- Synthesis and Catalytic Reactions
- CRISPR and Genetic Engineering
- Autophagy in Disease and Therapy
University of Warsaw
2014-2024
Instytut Biologii Doświadczalnej im. Marcelego Nenckiego
2021
Polish Academy of Sciences
2011-2021
Nowadays gene manipulation techniques ("DNA therapy") undergo progressive development and become widely used in industry medicine. Since new advances mRNA technologies are capable for obtaining particles with increased stability translational efficiency, RNA an attractive alternative advancement of DNA therapy. For the past years studies have been conducted to explore different modification cap structure its effect on properties. Recently we shown that at N2 position 7-methylguanosine leads...
Metazoan spliced leader (SL) trans -splicing generates mRNAs with an m 2,2,7 G-cap and a common downstream SL RNA sequence. The mechanism for eIF4E binding is unknown. Here, we describe the first structure of compare it to cognate 7 G-eIF4E complex. These structures Nuclear Magnetic Resonance (NMR) data indicate that nematode Ascaris suum binds two different caps in similar manner except loss single hydrogen bond on G-cap. Nematode mammalian both have low affinity compared G-cap, G-SL 22-nt...
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...
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...
Although the sporadic form of Alzheimer’s disease (AD) is prevalent form, cellular events underlying pathogenesis have not been fully characterized. Accumulating evidence points to mitochondrial dysfunction as one responsible for AD progression. We investigated function in fibroblasts collected from patients diagnosed with (sAD), placing a particular focus on turnover. measured biogenesis and autophagic clearance, evaluated presence bioenergetic stress sAD cells. The turnover was clearly...
The development of targeted anticancer drugs has been one the most challenging goals current research. Eukaryotic translation initiation factor 4E (eIF4E) is an oncogene that stimulates mRNA via binding to 5′ endcap structure. It well documented eIF4E overexpressed in many cancers including breast, prostate, head and neck, stomach malignancies leads oncogenic transformation metastasis. One approach block function cancer cells based on disruption interaction between cap structure using analog...
The technology of mRNA-based drugs is currently being intensively developed and implemented. Medical products this type are already used as viral vaccines could potentially find application in a wide range diseases. tremendous interest mRNA due to the relatively easy production process, which can be quickly adapted meet societal needs. properties molecule depend on structure its individual components, such cap at 5ʹ end. Modifications significantly affect translational potential lifespan...
mRNAs of primitive eukaryotes such as Caenorhabditis elegans and Ascaris summ possess two different caps at their 5′ terminus. They have either a typical cap which consists 7-methylguanosine linked via 5′,5′-triphosphate bridge to the first transcribed nucleotide (MMG cap) or an atypical hypermethylated form with additional methyl groups N2 position (TMG cap). Studies on interaction between end mRNA proteins that specifically recognize its structure been carried out for several years they...
Aryloxy triester phosphoramidate methodology, commonly known as ProTide technology, is one of the most widely used prodrug approaches applied to therapeutic nucleosides. This approach has been extensively by pharmaceutical industry and researchers in medicinal chemistry. Herein we report our adaptation this effective method for synthesis bioactive 5'-mRNA cap analogues inhibitors targeting cap-dependent translation. The was performed two main stages: preparation N2-modified guanosine their...
Abstract Here we present a systematic analysis of the synthesis unsymmetrical disulphides employing 6‐thioguanosine and its mono‐ dinucleotides by three most common strategies: nucleophilic substitution thiol, thiol exchange reaction with another disulphide oxidative dehydrogenation coupling reactions S−H bonds. The was found to be efficient approach could used not only for nucleosides but also nucleotides.
Alzheimer's disease (AD) is one of the most common neurodegenerative diseases. Only 10% all cases are familial form, remaining 90% sporadic form with unknown genetic background. The etiology AD still not fully understood. Pathogenesis and pathobiology this limited due to number experimental models. We used primary culture fibroblasts derived from patients diagnosed for investigation dynamic properties mitochondria, including fission-fusion process localization mitochondria within cell....
mRNA degradation is a key mechanism of gene expression regulation. In the 3' → 5' decay pathway, degraded by exosome complex and resulting cap dinucleotide or short-capped oligonucleotide hydrolyzed mainly decapping scavenger enzyme (DcpS)-a member histidine triad family. The similar for DcpS from different species; however, their respective substrate specificities differ. this paper, we describe experiments exploring activity human (hDcps), Caenorhabditis elegans (CeDcpS), Ascaris suum...