A5062805514- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Ubiquitin and proteasome pathways
- Cancer-related Molecular Pathways
- Crystallography and molecular interactions
- RNA Research and Splicing
- Historical and Archaeological Studies
- RNA and protein synthesis mechanisms
- Medieval European History and Architecture
- RNA modifications and cancer
- Geology and Environmental Impact Studies
- Synthesis and Characterization of Heterocyclic Compounds
- Protein Degradation and Inhibitors
- Peptidase Inhibition and Analysis
- Nutrition, Genetics, and Disease
- Cardiomyopathy and Myosin Studies
- Polish Historical and Cultural Studies
- Microtubule and mitosis dynamics
- Cancer, Hypoxia, and Metabolism
- Insect Resistance and Genetics
- HIV Research and Treatment
- Genetics and Neurodevelopmental Disorders
- HIV/AIDS drug development and treatment
- Click Chemistry and Applications
Jagiellonian University
2016-2024
University of Wrocław
2020
University of Groningen
2016
USP2a is a deubiquitinase responsible for stabilization of cyclin D1, crucial regulator cell-cycle progression and proto-oncoprotein overexpressed in numerous cancer types. Here we report that lithocholic acid (LCA) derivatives are inhibitors USP proteins, including USP2a. The most potent LCA derivative, hydroxyamide (LCAHA), inhibits USP2a, leading to significant Akt/GSK3β-independent destabilization but does not change the expression p27. This leads defects progression. As result, LCAHA...
The p53 pathway is inactivated in almost all types of cancer by mutations the encoding gene or overexpression negative regulators, Mdm2 and/or Mdmx. Restoration function inhibition p53-Mdm2/Mdmx interaction opens up a prospect for nongenotoxic anticancer therapy. Here, we present syntheses, activities, and crystal structures two novel classes Mdm2-p53 inhibitors that are based on 3-pyrrolin-2-one 2-furanone scaffolds. complexes formed these reveal dimeric protein molecular organization has...
The tumor suppressor protein p53, the "guardian of genome", is inactivated in nearly all cancer types by mutations TP53 gene or overexpression its negative regulators, oncoproteins MDM2/MDMX. Recovery p53 function disrupting p53-MDM2/MDMX interaction using small-molecule antagonists could provide an efficient nongenotoxic anticancer therapy. Here we present syntheses, activities, and crystal structures inhibitors based on 1,4,5-trisubstituted imidazole scaffold which are appended with...
By binding to the spliceosomal protein Snu66, human ubiquitin-like Hub1 is a modulator of spliceosome performance and facilitates alternative splicing. Small molecules that bind would be interest study protein-protein interaction Hub1/Snu66, which linked several pathologies, such as hypercholesterolemia, premature aging, neurodegenerative diseases, cancer. To identify small molecule ligands for Hub1, we used interface analysis, peptide modeling Hub1/Snu66 fragment-based NMR screening....
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Protein-protein interactions play a key role in cell homeostasis and physiological functions of the organisms. Consequently, their malfunction leads to diseases such as cancer, metastasis neurodegeneration. The Hub1/Snu66 interaction is responsible for controlling alternative splicing through non-covalent binding HIND (Hub1-Interacting Domain) domain Snu66 spliceosomal protein. To better understand how Hub1 works living organisms, we conducted study find small molecules that have an affinity...