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Using fragment-based technologies to target protein-protein interactions.

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 fragment-based 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.