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Target identification is the process of identifying the direct molecular target – for example protein or nucleic acid – of a small molecule. In clinical pharmacology, target identification is aimed at finding the efficacy target of a drug/pharmaceutical or other xenobiotic. The techniques used may be based on principles of biochemistry, biophysics, genetics, chemical biology or other disciplines.
Molecular glue degraders are small molecules that have major therapeutic potential. Here, protein microarrays enabled the identification of proteins that can be glued to the VHL E3 ligase and degraded with VHL targeting ligands.
Yeast surface display technology enables real-time monitoring and effective screening of libraries of millions of disulfide-cyclised peptides against diverse protein targets. Selected ligands are characterised rapidly and quantitatively without the need for chemical synthesis and purification.
Alpha-synuclein (aSyn) aggregation is implicated in Parkinson’s disease, yet the molecular mechanisms, particularly involving lipid interactions, remain poorly understood. Here, the authors develop a mathematical model incorporating nucleation-conversion-polymerization processes to elucidate aggregation dynamics upon aSyn-lipid interaction, offering insights into therapeutic strategies and advancing quantitative systems pharmacology for neurodegenerative diseases.
Molecular glue degraders are small molecules that have major therapeutic potential. Here, protein microarrays enabled the identification of proteins that can be glued to the VHL E3 ligase and degraded with VHL targeting ligands.
Structural biology is crucial in understanding disease mechanisms and in driving drug and vaccine development—applications that are particularly relevant to Africa’s challenges—yet Africa faces significant barriers to advancing structural biology. Here, the authors outline a recent capacity building workshop run by BioStruct-Africa, focused on training of artificial intelligence tools such as AlphaFold, designed to foster a highly skilled community of structural biologists in Africa.
A photoswitchable, DNA structure-specific small-molecule probe, named G4switch, has been developed for the reversible targeting of DNA G-quadruplexes (G4s) in vitro and within cells. This versatile chemical tool enables precise, light-controlled modulation of G4-mediated gene expression and cell proliferation.
Proton pump inhibitors, commonly prescribed for excessive gastric acid secretion, may lead to unexpected side effects. Now a chemoproteomic method enables a comprehensive profiling of their off-target interactions, offering valuable insights into their mechanism of action in living cells.
