Rationale and Objective
Today, the quality of crystallographic data and the general knowledge of structure-function relationships has progressed to such an extent that the rational design of ligands becomes a feasible objective.
Previously, many drugs were developed by trial and error, relying on chemical modifications to their structures. With greater and more detailed insight into the structure of membrane receptors, the rational design of drugs is fast becoming an issue that can be addressed. For this to become reality, we coordinate approaches to increase our knowledge of ligand-gated ion channel structure at high-resolution.
Neurocypres brings together 18 researchers and 4 companies from all over Europe in a large-scale integrated effort to capture such high-resolution structural information encompassing either the entire structure of selected receptors, or of specific functional domains in these receptors.
This project is of direct relevance to human health in view of the importance of this class of receptors as drug targets. Indeed, these receptors are pivotally involved in many debilitating diseases, such as, anxiety sleep disorders and cognitive dysfunction of learning and memory.
Funding provided by the European Union is used to establish new discovery projects in the field of nAChRs, GABAA and 5HT3 receptors. Additional projects are also dedicated to: understanding the fundamentals of receptor function; to revealing precise subunit stoichiometries for native receptors in the CNS; to analyzing the types and roles of receptor-associated proteins; and finally, to designing methods for promoting high-throughput electrophysiological analyses.
With these new approaches and the large body of information that will be obtained, we are exploring innovative ways of designing drugs to target new sites on receptors with the aim of understanding receptor-related diseases.