A5049519225- Microtubule and mitosis dynamics
- Enzyme Structure and Function
- 14-3-3 protein interactions
- Cancer therapeutics and mechanisms
- Microbial Applications in Construction Materials
- Advanced biosensing and bioanalysis techniques
- Synthesis and biological activity
- Microbial Natural Products and Biosynthesis
- Photochromic and Fluorescence Chemistry
- Computational Drug Discovery Methods
- Radical Photochemical Reactions
- bioluminescence and chemiluminescence research
- Carbohydrate Chemistry and Synthesis
- Cancer Mechanisms and Therapy
- Cancer Treatment and Pharmacology
- Photosynthetic Processes and Mechanisms
- Biochemical and Molecular Research
- Machine Learning in Materials Science
- Pneumocystis jirovecii pneumonia detection and treatment
- DNA Repair Mechanisms
- Porphyrin Metabolism and Disorders
- DNA and Nucleic Acid Chemistry
- Cystic Fibrosis Research Advances
- CRISPR and Genetic Engineering
- Protein Structure and Dynamics
Italian Institute of Technology
2020-2023
University of Bologna
2017
Abstract Tubulin plays essential roles in vital cellular activities and is the target of a wide range proteins ligands. Here, using combined computational crystallographic fragment screening approach, we addressed question how many binding sites exist tubulin. We identified 27 distinct sites, which 11 have not been described previously, analyzed their relationship to known tubulin–protein tubulin–ligand interactions. further observed an intricate pocket communication network 56 chemically...
The binding and release of ligands from their protein targets is central to fundamental biological processes as well drug discovery. Photopharmacology introduces chemical triggers that allow the changing ligand affinities thus activity by light. Insight into molecular mechanisms photopharmacology largely missing because relevant transitions during light-triggered reaction cannot be resolved conventional structural biology. Using time-resolved serial crystallography at a synchrotron X-ray...
Synthetic lethality is an innovative framework for discovering novel anticancer drug candidates. One example the use of PARP inhibitors (PARPi) in oncology patients with BRCA mutations. Here, we exploit a new paradigm based on possibility triggering synthetic using only small organic molecules (dubbed "fully small-molecule-induced lethality"). We exploited this to target pancreatic cancer, one major unmet needs oncology. discovered dihydroquinolone pyrazoline-based molecule (35d) that...
In this study, we capitalized on our previously performed crystallographic fragment screen and developed the antitubulin small molecule Todalam with only two rounds of straightforward chemical synthesis. binds to a novel tubulin site, disrupts microtubule networks in cells, arrests cells G2/M, induces cell death, synergizes vinblastine. The compound destabilizes microtubules by acting as molecular plug that sterically inhibits curved-to-straight conformational switch α-tubulin subunit,...
In cystic fibrosis (CF), deletion of phenylalanine 508 (F508del) in the CF transmembrane conductance regulator (CFTR) is associated to misfolding and defective gating mutant channel. One most promising drug targets ubiquitin ligase RNF5, which promotes F508del-CFTR degradation. Recently, first ever reported inhibitor RNF5 was discovered, i.e., 1,2,4-thiadiazol-5-ylidene inh-2. Here, we designed synthesized a series new analogues explore structure–activity relationships (SAR) this class...
Transition metals are both essential micronutrients and limited in environmental availability. The Ni(II)-dependent urease protein, the most efficient enzyme known to date, is a paradigm for studying strategies that cells use handle an essential, yet toxic, metal ion. Urease virulence factor of several human pathogens, addition decreasing efficiency soil organic nitrogen fertilization. Ni(II) insertion active site performed through action three accessory proteins: UreD, UreF, UreG. crystal...
RAD51 is an ATP-dependent recombinase, recruited by BRCA2 to mediate DNA double-strand breaks repair through homologous recombination and represents attractive cancer drug target. Herein, we applied for the first-time protein-templated dynamic combinatorial chemistry on as a hit identification strategy. Upon design of N-acylhydrazone-based libraries, showed clear templating effect, amplifying 19 N-acylhydrazones. Screening against RAD51-BRCA2 protein-protein interaction via ELISA assay...
Urease is a nickel-containing enzyme that essential for the survival of several and often deadly pathogenic bacterial strains, including Helicobacter pylori. Notwithstanding attempts, development direct urease inhibitors without side effects human host remains, to date, elusive. The recently solved X-ray structure HpUreDFG accessory complex involved in activation opens new perspectives structure-based drug discovery. In particular, quaternary assembly presence internal tunnels nickel...
Abstract Tubulin plays essential roles in vital cellular activities and is the target of a wide range proteins ligands. Here, using combined computational crystallographic fragment screening approach, we addressed question how many binding sites exist tubulin. We identified 27 distinct sites, which 11 have not been described previously, analyzed their relationship to known tubulin–protein tubulin–ligand interactions. further observed an intricate pocket communication network 56 chemically...
Abstract In this study, we capitalized on our previously performed crystallographic fragment screen and developed the antitubulin small molecule Todalam with only two rounds of straightforward chemical synthesis. binds to a novel tubulin site, disrupts microtubule networks in cells, arrests cells G2/M, induces cell death, synergizes vinblastine. The compound destabilizes microtubules by acting as molecular plug that sterically inhibits curved‐to‐straight conformational switch α‐tubulin...
Abstract The binding and release of ligands from their protein targets is central to fundamental biological processes as well drug discovery. Photopharmacology introduces chemical triggers that allow the changing ligand affinities thus activity by light. Insight into molecular mechanisms photopharmacology largely missing because relevant transitions during light-triggered reaction cannot be resolved conventional structural biology. Using time-resolved serial crystallography at a synchrotron...
Abstract The binding and release of ligands from their protein targets is central to fundamental biological processes as well drug discovery. Photopharmacology introduces chemical triggers that allow the changing ligand affinities thus activity by light. Insight into molecular mechanisms photopharmacology largely missing because relevant transitions during light-triggered reaction cannot be resolved conventional structural biology. Using time-resolved serial crystallography at a synchrotron...