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In a series of scientific publications leadXpro AG scientists explore the utility of cutting-edge X-ray technologies for the discovery of new therapeutics.

Medicines prescribed in ten years’ time to treat cancer, infectious and many other diseases are being developed nowadays with the help of sophisticated 3D atomic-resolution imaging technologies. Researchers at leadXpro, a young biotech company at PARK INNOVAARE, and their collaborators showcase in two publications (see the links on the right) the power of new atomic-resolution protein 3D structure determination serial crystallography and free electron lasers. As a test case the Adenosine receptor A2A was employed, a promising drug target that may hold the key to treating specific forms of cancer. With the help of these new imaging technologies, leadXpro researchers can see the precise interactions of new potential drug molecules, utilizing data from experiments that are conducted at ambient temperature and with X-ray Free Electron Lasers (XFELs) which are billion-fold more brilliant compared to 3rd generation synchrotrons.

Robert Cheng, Principal Scientist at leadXpro says: “At ambient temperature, the three-dimensional protein structures we obtain are more physiologically relevant to those in the human body. We can see minute structural dynamics that are often invisible with the traditional approach of freezing samples at minus 173 degrees Celsius. In some cases, we can discover novel opportunities to block disease-relevant protein targets. This helps us to design better drug molecules.“

Serial crystallography with the new XFEL technology will soon become available for leadXpro scientists at the SwissFEL of the Paul Scherrer Institute (PSI). Advantages include successful structure determination for difficult-to-grow membrane protein crystals of key therapeutic drug targets, higher resolution and improved quality of the structural information, the absence of radiation damage and the ability of full automation of crystal delivery and data collection. No other researchers in the world, other than those at leadXpro, can currently combine the new serial crystallography approach with XFEL for proprietary drug discovery research. With this technology in hand, ‘novel chemotypes’, with pronounced specificity and efficacy will be discovered for highly challenging systems such as transmembrane receptors, transporters and ion channels. With the new SwissFEL right next door, leadXpro has excellent conditions to discover new generations of medicines to treat patients in the future.