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Targeted Stabilizers of Protein-Protein Interactions as a Novel Class of Therapeutic Agents and Basic Research Tool Compounds

Dario Valenti, Stanimira Hristeva, Anna Karawajczyk, Dimitrios Tzalis

Taros, TASPPI

Abstract:

Protein-protein interactions (PPIs) are involved in a wide range of human biological processes and related possible pathologies.
Therefore, PPIs’ modulation by small molecules is a crucial topic in drug discovery. Modulation of protein-protein interactions means to push the equilibrium between the free proteins and the complex toward one of these two states (Figure 1). There are two strategies to accomplish that: inhibition and stabilisation.
In contrast to the inhibition of PPIs, the stabilisation approach has not yet been exploited in a systematic way. Thus, the TASPPI consortium is aiming to identify chemical stabilizers for providing new crucial therapeutic strategies in the Horizon 2020 key areas of “Ageing Population” (neurodegeneration and cancer) and “Increased Burden of Chronic Diseases” (metabolic disorders and inflammation). The main targets of the consortium are 14-3-3 protein and its complexes with different protein partners.

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