CD Laboratory for Entropy Oriented Drug Design

This CD Laboratory researches novel, rigid therapeutic agents that fit precisely into your target protein like a security key. It designs precisely fitting molecules and synthesises them precisely in their three-dimensional structure.

Many therapeutic agents work according to the lock-and-key principle, whereby the active ingredient binds as precisely as possible to the receptor of a protein and inhibits it. In order for such a key to fit precisely into the lock and maximise its effectiveness, it should retain its shape as far as possible and not be able to adopt a different, less effective conformation by twisting its molecular structure. The number of rotatable bonds within a molecule is referred to as the degree of conformational entropy. Single bonds between two atoms can usually rotate freely. If the bonds between the atoms are strengthened, e.g. by double bonds, or if entire ring systems are merged, the structures become increasingly rigid.

This CD Laboratory pursues a novel approach to drug development that follows these principles and is called entropy-orientated drug design (EnODD). EnODD focuses on designing, synthesising and validating rigid compounds based on fused ring systems with minimal flexibility right at the beginning of the development process. As this minimises entropic losses, i.e. the number of keys that do not fit because they are twisted, this new strategy makes it possible to develop potent active substances for disease-causing proteins that have not yet been treated.

To ensure the success of the EnODD strategy, precise active ingredient design and expertise in the organic synthesis of complex molecular constructs with a very precise 3D structure are required. Molecular scaffolds based on natural models, but also completely new structures can be created. This CD Laboratory is researching the principle of EnODD using certain protein families that were previously considered "undruggable", i.e. locks for which no suitable keys could be found.