A5004984858- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Hybrid Renewable Energy Systems
- Estrogen and related hormone effects
- RNA and protein synthesis mechanisms
- Cancer-related molecular mechanisms research
- Chemical Synthesis and Analysis
- Semiconductor materials and devices
- thermodynamics and calorimetric analyses
- Cancer-related gene regulation
- Click Chemistry and Applications
- Reproductive System and Pregnancy
- Histone Deacetylase Inhibitors Research
- CRISPR and Genetic Engineering
- Virology and Viral Diseases
- HIV Research and Treatment
- Nanopore and Nanochannel Transport Studies
- Viral Infectious Diseases and Gene Expression in Insects
- Mosquito-borne diseases and control
- MicroRNA in disease regulation
- Synthesis and Biological Evaluation
- Field-Flow Fractionation Techniques
- DNA and Nucleic Acid Chemistry
- Immunotherapy and Immune Responses
Johannes Gutenberg University Mainz
2022-2025
Institute of Molecular Biology and Genetics
2019
National Academy of Sciences of Ukraine
2019
The human RNA methyltransferase DNMT2 is thought to be involved in various pathophysiological processes, yet, a major challenge drug targeting given by the fact that current SAH-derived inhibitors have poor target selectivity and limited cellular permeability. In this study, we performed DNA-encoded library (DEL) screening on yielding five non-SAH-like hit structures, three of which feature peptidomimetic scaffold. All DEL hits could validated orthogonal biophysical biochemical assays for...
Developing methyltransferase inhibitors is challenging, since most of the currently used assays are time-consuming and cost-intensive. Therefore, efficient, fast, reliable methods for screenings affinity determinations utmost importance. Starting from a literature-known fluorescent S-adenosylhomocysteine derivative, 5-FAM-triazolyl-adenosyl-Dab, developed fluorescence polarization assay to investigate histone mixed-lineage leukemia 1, we herein describe applicability this compound as tracer...
Targeting RNA methyltransferases with small molecules as inhibitors or tool compounds is an emerging field of interest in epitranscriptomics and medicinal chemistry. For two challenging that introduce the 5-methylcytosine (m5C) modification different tRNAs, namely DNMT2 NSUN6, ultra-large commercially available chemical space was virtually screened by physicochemical property filtering, molecular docking, clustering to identify new ligands for those enzymes. Novel chemotypes binding NSUN6...
The DNA methyltransferase 2 (DNMT2) is an RNA modifying enzyme associated with pathophysiological processes, such as mental and metabolic disorders or cancer. Although the development of inhibitors remains challenging, DNMT2 not only a promising target for drug discovery, but also activity-based probes. Here, we present covalent SAH-based decorated new type aryl warhead. Based on noncovalent inhibitor N-benzyl substituent, Topliss scheme was followed optimization. results showed that...
Abstract RNA methyltransferases (MTases) have recently become increasingly important in drug discovery. Yet, most frequently utilized MTase assays are limited their throughput and hamper this rapidly evolving field of medicinal chemistry. This study developed a microscale thermophoresis (MST)-based split aptamer assay for enzymatic investigations, improving current methodologies by offering non-proprietary, cost-effective, highly sensitive approach. Our findings demonstrate the assay’s...
Chemical modifications on cellular and viral RNAs are new layers of post-transcriptional regulation processes including RNA stability translation. Although advances in analytical methods have improved detection sensitivity, the precise mapping at single-base resolution remains challenging. Especially for low abundant extracted from infected cells, requirements sensitivity purity limit accuracy reproducibility. Here we report two-step method ViREn enrichment genomic (gRNA) dengue virus...
Abstract Die Methylierung von RNA ist ein Stoffwechselprozess, der für seine Verbindung zu verschiedenen Krankheiten bekannt geworden ist. Darum gewinnen RNA‐Methyltransferasen (MTasen) in Arzneistoffentwicklung zunehmend an Bedeutung. gängigsten RNA‐MTase‐Assays sind jedoch ihrem Durchsatz begrenzt, was die Entwicklung im dynamischen Forschungsfeld medizinischen Chemie verlangsamt. In dieser Studie präsentieren wir modulares Synthesesystem Nanomolmaßstab, dass Identifizierung...
Abstract RNA methylation is a metabolic process validated for its association with various diseases, and thus, methyltransferases (MTases) have become increasingly important in drug discovery. Yet, most frequently utilized MTase assays are limited their throughput hamper this rapidly evolving field of medicinal chemistry. In study, we describe modular nanomole scale building block system that allowed the identification tailored fluorescent probes to unlock broad selection targets...
Aim. The repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) plays a dual role. It protects cell against DNA’s alkylation and death. But in the case of cancer treatment it provides cells’ resistance to alkylating chemotherapy. So is important regulate MGMT activity inhibit cells activate normal cells. To treat some type cancers used combination chemotherapy hormone therapy. So, we tried investigate role estrogen on transcription. Methods. We performed western-blot RT-qPCR analyse...
To determine whether the steroid hormone β-estradiol affects transcription of human MGMT gene. The expression status DNA repair enzyme O (6)-methylguanine-DNA methyltransferase (MGMT) is important when planning treatment patients with oncology, because its presence in tumor cells may reduce effectiveness alkylating chemotherapy. Alkylating chemotherapy combined therapy tumors, so study effect on number transcripts gene vitro has not only theoretical and also practical significance. Methods....
Aims: to investigate the steroid hormone progesterone effect on human MGMT gene expression at mRNA and protein levels in cell lines with different patterns of nuclear receptors membrane receptor PGRMC1. Methods: culture, RNA / isolation, cDNA synthesis, real-time polymerase chain reaction, Western blot analysis. Results: We observe upregulation by both levels. Conclusions is more complex than direct regulation through classical receptor.Keywords: O6-methylguanine-DNA methyltransferase...