Georgiou, Charis; McNae, Iain; Wear, Martin; Ioannidis, Harris; Michel, Julien; Walkinshaw, Malcolm published the artcile< Pushing the Limits of Detection of Weak Binding Using Fragment-Based Drug Discovery: Identification of New Cyclophilin Binders>, Category: pyridine-derivatives, the main research area is drug design diaminopyridine cyclophilin binding; PPIases; cyclophilin inhibitors; fragment-based drug discovery; free energy calculations; protein–ligand X-ray crystallography.
Fragment-based drug discovery is an increasingly popular method to identify novel small-mol. drug candidates. One of the limitations of the approach is the difficulty of accurately characterizing weak binding events. This work reports a combination of X-ray diffraction, surface plasmon resonance experiments and mol. dynamics simulations for the characterization of binders to different isoforms of the cyclophilin (Cyp) protein family. Although several Cyp inhibitors have been reported in the literature, it has proven challenging to achieve high binding selectivity for different isoforms of this protein family. The present studies have led to the identification of several structurally novel fragments that bind to diverse Cyp isoforms in distinct pockets with low millimolar dissociation constants A detailed comparison of the merits and drawbacks of the exptl. and computational techniques is presented, and emerging strategies for designing ligands with enhanced isoform specificity are described.
Journal of Molecular Biology published new progress about Cyclophilins Role: BSU (Biological Study, Unclassified), BIOL (Biological Study) (inhibitors). 212268-13-8 belongs to class pyridine-derivatives, and the molecular formula is C5H6FN3, Category: pyridine-derivatives.