Fragment-screening by X-ray crystallography at MAX IV on a human oncology-related protein

Important results from the project

In this project, Sprint Bioscience, through the guidance and the support of the FragMAX team at BioMAX (MAX IV), aimed to acquire the expertise required to use X-ray screening by crystallography (XFS) as a fragment-screening method and to use this novel expertise to identify new starting points to an oncology-related protein. All goals were successfully achieved: screening campaign and data analysis were performed following state-of-the-art methodologies and a large set of new starting points were obtained against the target protein.

Expected long term effects

A fragment-library with properties suitable for XFS has been specially designed by Sprint Bioscience for this project. The crystal system has been extensively optimized to meet the requirements for throughput and quality. The tools available at BioMAX allowed the XFS campaign (including analysis) to be performed in slightly more than one week. Analysis through the pipeline developed by FragMAX gave a high hit-rate of about 20%. These hits will be used in the Sprint Bioscience chemistry program.

Approach and implementation

This project was divided into three complementary phases: library creation, optimization of the crystal system, XFS campaign. While the two first ones could overlap in time, it was essential that they were both successfully achieved before starting the last one. While the project is considered as overall very successful and that each phase managed to respect the time it was granted, some additional steps would be introduced in future XFS campaign to further increase the number of hits generated.