Accelerating Drug Discovery - Diversity Oriented Synthesis of Fragment Libraries
Name of applicant
Nikolaj Lilholm Villadsen
Amount
DKK 350,000
Year
2017
Type of grant
Internationalisation Fellowships
What?
The overall aim is to invent an improved strategy for fragment library synthesis to accelerate drug discovery. The pharmaceutical industry has called upon chemists to invent novel strategies to construct molecular fragments of high diversity that are easy to modify. We will develop novel strategies to construct a fragment library that fulfil those demands. Despite being a "proof-of-concept" project, we expect to discover novel small-molecule of great interest for the academic community and pharmaceutical industry.
Why?
As life expectancies increase, so does the need for new treatments for the aging population. To understand the underlying causes of human disease, researchers require chemical tools to understand human cell biology. Fragment based drug discovery is a state-of-the-art approach to generate lead compounds for drug discovery, and to invent chemical probes. More diverse fragments will target a broader range of targets, and easy modifiable fragments will accelerate follow-up studies.
How?
The research will be conducted at the University of Cambridge in the lab of Professor David Spring. We plan to synthesise a small library of fragments by a novel strategy. This library will be evaluated for binding affinity towards a panel of proteins via cutting edge automated protein X-ray facilities. Analysis of the fragment-protein binding site will guide a rational synthesis of a 2nd generation fragment library with improved binding energy. By following this strategy, we expect to discover small-molecules that are applicable as lead structure(s) for drug development efforts or as high quality chemical probes with novel targets. Our research will function as a "proof-of-concept" study to demonstrate that fragment quality and diversity can increase by our ideas.