Peak Proteins presented details of a successful collaboration with Sygnature Discovery at the International Medicinal Chemistry Symposium in Manchester last week. The project involved looking at the interactions of small molecule fragments with a bromodoamin protein (BRD3). The modes of binding of these fragments were determined using X-ray crystallography.
An inital Surface Plasma Resonace screen was carried out to identify suitable fragments from Sygnature’s in-house fragment library. Subsequently, the number of hit molecules was reduced to smaller set using additional criteria. BRD3 crystals were soaked with the compounds and x-ray data collected to determine the crystal structure. In the first round of experiments, Peak Proteins were able to unambiguously identify the binding of 6 of these compounds, from a shortlist of 9. This was an impressive success rate for fragment based structural determination. Also, this approach, demonstrated the importance of reliably confirming fragment binding before undertaking x-ray experiments.
The poster link below shows these protein structures, and further experiemental details.
BRD3 FBLG EFMC-ISMC August 2016