Dissertation
No strings attached: advancing drug discovery through barcode-free screening of massive chemical libraries
Discovering new bioactive molecules is crucial for drug development. Finding a hit compound for a new drug target usually requires screening of millions of molecules.
- Author
- E.A. van der Nol
- Date
- 12 June 2026
- Links
- Thesis in Leiden Repository
This thesis provides an overview of current screening methods and introduces a self-encoded library (SEL) platform, which enables the direct screening of more than half a million small molecules in a single experiment.
This platform integrates tandem mass spectrometry with novel software for automated structure annotation, allowing for the synthesis and screening of a wide range of chemical structures. The expansion of this SEL platform through a Buchwald-Hartwig-based library demonstrates that complex chemical reactions can be easily integrated into SELs, which significantly increases the chemical diversity of the system. Through the application of this method, several potent inhibitors and binders have already been discovered.
The developed SEL platform offers a new strategy to accelerate the early phases of drug discovery and serves as a complementary technique to existing screening techniques. The ability to screen barcode-free libraries of this magnitude opens new doors for previously inaccessible target classes. It is expected that this research will grow into a broadly applicable methodology that is useful in both academic and industrial settings for the accelerated discovery of new therapeutic ligands.