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

Reference number
Coordinator Sprint Bioscience AB - SprintBioscience
Funding from Vinnova SEK 392 202
Project duration June 2019 - June 2020
Status Completed
Venture Research infrastructure - utilisation and collaboration
Call Industrial pilot projects for utilisation of neutron- and photon based techniques at large scale infrastructures - spring 2019

Purpose and goal

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 results and 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.

Planned 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.

The project description has been provided by the project members themselves and the text has not been looked at by our editors.

Last updated 17 July 2020

Reference number 2019-02567

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