Overcoming the Limitations of Fragment Merging: Rescuing a Strained Merged Fragment Series Targeting Mycobacterium tuberculosis CYP121

• DOI: 10.1002/cmdc.201300219
• Publication Date: 2013-06-20T17:28:18Z
• Authors: Sean A. Hudson; Sachin Surade; Anthony G. Coyne; Kirsty J. McLean; David Leys; Andrew W. Munro; Chris Abell
• Keywords: Fragment (logic); Merge (version control); Ligand efficiency

Freedom to merge: A combination of crystal structure examination and in silico predictions made it possible overcome the conformational limitations fragment merging escape internal strain a series weakly binding merged fragments that target M. tuberculosis CYP121. The insights attained provide new perspective guide for prioritizing synthetic efforts toward future ongoing fragment-based ligand discovery campaigns.