A5022730107- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- RNA Research and Splicing
- Crystallization and Solubility Studies
- Carbohydrate Chemistry and Synthesis
- Computational Drug Discovery Methods
- DNA and Nucleic Acid Chemistry
- Biochemical and Molecular Research
- PI3K/AKT/mTOR signaling in cancer
- X-ray Diffraction in Crystallography
- Enzyme Structure and Function
- Fluorine in Organic Chemistry
- Crystallography and molecular interactions
- Molecular spectroscopy and chirality
- Monoclonal and Polyclonal Antibodies Research
- RNA Interference and Gene Delivery
- Crystal structures of chemical compounds
- Cancer, Hypoxia, and Metabolism
- Metabolism, Diabetes, and Cancer
- Inflammatory mediators and NSAID effects
- Biopolymer Synthesis and Applications
- Calcium Carbonate Crystallization and Inhibition
- RNA regulation and disease
- Structural and Chemical Analysis of Organic and Inorganic Compounds
- Transgenic Plants and Applications
University of Warsaw
2014-2025
Instytut Farmaceutyczny
2022
University of California, San Francisco
2016
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...
Abstract The conserved decapping enzyme Dcp2 recognizes and removes the 5′ eukaryotic cap from mRNA transcripts in a critical step of many cellular RNA decay pathways. is dynamic that functions concert with essential activator Dcp1 diverse set coactivators to selectively efficiently decap target mRNAs cell. Here we present 2.84 Å crystal structure K . lactis Dcp1–Dcp2 complex Edc1 Edc3, substrate analog bound active site. Our shows how catalytically conformation enzyme, coactivator forms...
Quantum crystallography methods have been employed to investigate complex formation between nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase (COX) enzymes, with particular focus on the COX-1 COX-2 isoforms. This study analyzed electrostatic interaction energies of selected NSAIDs (flurbiprofen, ibuprofen, meloxicam celecoxib) active sites COX-2, revealing significant differences in binding profiles. Flurbiprofen exhibited strongest interactions both indicating its potent...
Ubiquitin-specific proteases (USPs) play crucial roles in cellular processes and have emerged as promising therapeutic targets for various diseases, including cancer. This study utilizes a multi-faceted computational approach to investigate...
Metazoan replication-dependent histone mRNAs are only present in S-phase, due partly to changes their stability. These end a unique stem-loop (SL) that is required for both translation and cell-cycle regulation. Previous studies showed mRNA degradation occurs through 5'→3' 3'→5' processes, but the relative contributions not known. The 3' of oligouridylated during its degradation, although it known whether this an essential step. We introduced firefly luciferase reporter containing UTR SL...
We describe a general method for the elongation of nucleoside oligophosphate chains by means cyanoethyl (CE) phosphorimidazolides. Though requires phosphorylation and subsequent deprotection reaction, both steps could be achieved in one pot without isolation/purification initial product. have also found that pyrophosphate bond formation this is significantly accelerated microwave irradiation.
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...
Dcp1/2 is the major eukaryotic RNA decapping complex, comprised of enzyme Dcp2 and activator Dcp1, which removes 5′ m 7 G cap from mRNA, committing transcript to degradation. activity crucial for quality control turnover, deregulation these processes may lead disease development. The molecular details catalysis remain elusive, in part because both substrate (m GpppN) GDP product are bound by with weak (mM) affinity. In order find inhibitors use elucidating catalytic mechanism Dcp2, we...
The results of structural studies on a series halogen-substituted derivatives 2-deoxy-D-glucose (2-DG) are reported. 2-DG is an inhibitor glycolysis, metabolic pathway crucial for cancer cell proliferation and viral replication in host cells, interferes with D-glucose D-mannose metabolism. Thus, its considered as potential anticancer antiviral drugs. X-ray crystallography shows that halogen atom present at the C2 position pyranose ring does not significantly affect conformation. However, it...
The structural studies on two bromo-substituted derivatives of 2-deoxy-d-glucose (2-DG), namely 2-deoxy-2-bromo-d-glucose (2-BG) and 2-deoxy-2-bromo-d-mannose (2-BM) are described. 2-DG itself is an inhibitor hexokinase, the first enzyme in glycolysis process, playing a vital role both cancer cell metabolism viral replication host cells. Because that, considered as potential anti-cancer anti-viral drugs. An X-ray quantum crystallography approach allowed us to obtain more accurate positions...
Protonation changes the molecular architecture of crystal structures, and thus modifies intermolecular interactions in studied structures.
Background: One defining feature of various aggressive cancers, including glioblastoma multiforme (GBM), is glycolysis upregulation, making its inhibition a promising therapeutic approach. compound 2-deoxy-d-glucose (2-DG), d-glucose analog with high clinical potential due to ability inhibit glycolysis. Upon uptake, 2-DG phosphorylated by hexokinase 2-DG-6-phosphate, which inhibits and downstream glycolytic enzymes. Unfortunately, use limited poor pharmacokinetics, suppressing efficacy....
Plants are able to produce various types of crystals through metabolic processes, serving functions ranging from herbivore deterrence photosynthetic efficiency. However, the structural analysis these has remained challenging due their small and often imperfect nature, which renders traditional X-ray diffraction techniques unsuitable. This study explores use Microcrystal Electron Diffraction (microED) as a novel method for plant-derived microcrystals, focusing on
Protein aggregation is a well-recognized problem in industrial preparation, including biotherapeutics. These low-energy states constantly compete with native-like conformation, which more pronounced the case of macromolecules low stability solution. A better understanding structure and function such aggregates generally required for rational development therapeutic proteins, single-chain fusion cytotoxins to target specific receptors on cancer cells. Here, we identified purified particles as...