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Basel researchers facilitate new libraries for drug discovery

Researchers at the University of Basel have developed an approach for building up new substance libraries. These will support the discovery of new medicines.

An artistic depiction of a macrocycle binding to a target protein. Image Credit:University of Basel, Basilius Sauter
An artistic depiction of a macrocycle binding to a target protein. Image Credit:University of Basel, Basilius Sauter

Some of our most potent medicines are made from natural products. These include macrocycles, which are hard to emulate in laboratories on account of their size and complexity. To find new lead compounds in drug research, huge libraries with diverse structures are required.

Researchers at the University of Basel have now developed a new approach that should help achieve just that. They have enabled a great variety of macrocycles to be synthesized and created a library of more than one million different molecules.

The researchers’ synthesis is based on the split-and-pool principle, as the University explains in a press release. Before a synthesis step, the whole library is split. Then each fraction is coupled with one of various building blocks and the newly built molecules are labeled with a covalently attached DNA sequence. Before the next synthesis step all fractions are pooled again.

This approach facilitates easier searches, because all 1.4 million members of the pooled library can be screened in a single experiment. Next generation DNA sequencing on the selected libraries could then identify macrocycles that bind target proteins.

„With a large diverse collection of macrocycles available for screening, a more data-rich investigation of the properties of these extraordinary molecules can begin“, comments Dennis Gillingham, Professor at the University of Basel. „This might reveal future medicinal applications, targets or active principles.“

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