TEMPLAPEPT: Template-directed stapling: towards functional helical peptides

Extended project summary:

The molecular basis of many diseases is not fully understood yet. This is the case for diseases which have attracted a lot of attention, such as cancer or neurodegenerative diseases, but also for rare diseases with small patient populations, dampening commercial interest in the development of treatments or diagnostic devices. Innovative approaches are therefore still needed to break the limits in understanding, at the chemical level, key biological processes. Success in this direction will provide groundbreaking information for developing new therapeutic agents.

Misregulation of protein-protein and carbohydrate-protein interactions is often implicated in disease states, constituting promising therapeutic targets. The aim of the TEMPLAPEPT project is to develop a novel technology as a platform for the study of these interactions beyond current knowledge. In particular, this project proposes a novel methodology for the stabilization of helical peptides, key structural element involved in a significant population of protein-protein and carbohydrate-protein interactions. This technology is based on the use of the α-helix structure as template for choosing the optimal helicity inducers and will also serve to engineer interesting properties in these peptide conjugates, not accessible by current methods. This is a general technology applicable to virtually any relevant target in which protein-protein and carbohydrate-protein interactions are involved, offering a broad scope of potential biological applications. Moreover, immobilization of helical scaffolds onto surfaces will allow the study of multivalency in such binding events, essential to control their affinity and selectivity.

This is a multidisciplinary project, combining organic and medicinal chemistry with biophysical and structural techniques. It is strongly based on the researcher’s background in synthetic supramolecular chemistry and molecular recognition.