Modern screening libraries comprise predominantly of 'flat', aromatic compounds. However, biological molecules often perform their function through the use of the precise, three-dimensional placement of their amino acid sidechains, enabling catalysis or binding to substrate or receptor. Many traditional screening campaigns performed industrially are thought to miss important three-dimensional interactions with protein targets, due to the planarity of the molecules which are screened, and often have low hit rates. To combat this, academic groups aimed to develop efficient methods to synthesis highly diverse, 'three-dimensional' molecules to enrich compound collections and therefore increase the chances of picking up complementary interactions with highly three-dimensional biomolecules.
Diversity-Oriented Synthesis (DOS) has been a central focus of the Spring Group for over two decades. Using simple, commercially-available building blocks and applying to them a broad range of diversifying chemistry, libraries of structurally diverse and stereochemically complex molecules have been produced. These have been used to enhance screening collections and have led to several hits in assays run here at the University of Cambridge, and further afield. A subset of the compounds is also available for plating with XChem at the Diamond Light Source.
If you would like to use our collection as part of a screen, both assay-based or computationally, do not hesitate to get in touch.