A5073558803- Carbohydrate Chemistry and Synthesis
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Click Chemistry and Applications
- ATP Synthase and ATPases Research
- Signaling Pathways in Disease
- Lysosomal Storage Disorders Research
- Chemical Synthesis and Analysis
- Biochemical and Molecular Research
- Studies on Chitinases and Chitosanases
- Mitochondrial Function and Pathology
- Ubiquitin and proteasome pathways
- Enzyme Production and Characterization
- Peptidase Inhibition and Analysis
University College London
2024
Universidad Loyola Andalucía
2024
Universidad de Sevilla
2018-2022
Two libraries of mono- and dimeric pyrrolidine iminosugars were synthesized by CuAAC (thio)urea-bond-forming reactions from the respective azido/aminohexylpyrrolidine iminosugar precursors. The resulting monomeric compounds screened for inhibition β-N-acetylglucosaminidase Jack beans, plant ortholog human lysosomal hexosaminidases. A selection best inhibitors these was then evaluated against β-N-acetylhexosaminidase B (hHexB) nucleocytoplasmic (hOGA). This evaluation identified a potent (nM)...
ABSTRACT Targeted protein degradation (TPD) has opened new opportunities to investigate signalling pathways as a research tool, and unique therapeutic strategy using bifunctional chimeric small molecules, with candidate molecules in clinical trials for the treatment of breast cancer prostate cancer. Most current TPD approaches use 26S proteasomal machinery via PROteolysis TArgeting Chimeras (PROTACs), however, emerging strategies autophagy system, termed AUtophagy (AUTACs) expand on degrader...
The parallel synthesis of a 26-membered-library aromatic/aliphatic-(thio)urea-linked pyrrolizidines followed by in situ biological evaluation toward α-galactosidases has been carried out. combination the (thio)urea-forming click reaction and screening is pioneer search for glycosidase inhibitors allowed discovery potent coffee bean α-galactosidase inhibitor (IC50 = 0.37 μM, Ki 0.12 μM) that also showed inhibition against human lysosomal (α-Gal A, IC50 5.3 4.2 μM).
Macrocyclic drugs can address an increasing range of molecular targets but enabling central nervous system (CNS) access to these has been viewed as intractable problem. We designed and synthesized a series quinolinium-modified cyclosporine derivatives targeted the mitochondrial cyclophilin D protein. Modification cation enable greater delocalization was confirmed by x-ray crystallography cations. Critically, improved brain concentrations. Assessment compounds in preclinical assays for...