Whilst fragment-based screening has found significant utility in aiding the discovery of high quality hits against a range of targets,
the use of this technology in the protein-protein interaction inhibitor field is very much in its infancy. This review aims to highlight
the key technologies used to identify fragment hits, such as NMR, SPR, X-ray crystallography and biochemical screening, the fragmentbased
protein-protein interaction case studies reported to date and, more importantly, the potential of this methodology in unearthing high
quality hit molecules in this critical area of drug discovery. In addition, we also discuss some of the key aspects of fragment library design,
the composition of a high quality library and suggest ways in which future, more structurally diverse fragments which occupy different
regions of chemical space to the vast majority of current fragment libraries may be selected.
Keywords: Fragment-based drug discovery, protein-protein interactions, hot spots, ligand efficiency, biophysical, techniques, inhibitors, fragment libraries, diversity, NMR.
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Published on: 23 August, 2012
Page: [4685 - 4696]