Freedom to merge: A combination of crystal structure examination and in silico predictions made it possible to overcome the conformational limitations of fragment merging and escape the internal strain in a series of weakly binding merged fragments that target M. tuberculosis CYP121. The insights attained provide a new perspective and guide for prioritizing synthetic efforts toward fragment merging in future and ongoing fragment‐based ligand discovery campaigns.
Hudson, S. A., Surade, S., Coyne, A. G., Mclean, K. J., Leys, D., Munro, A. W., & Abell, C. (2013). Overcoming the Limitations of Fragment Merging: Rescuing a Strained Merged Fragment Series Targeting Mycobacterium tuberculosis CYP121. ChemMedChem, 8(9), 1451-1456. https://doi.org/10.1002/cmdc.201300219