Set-up and screening of a fragment library targeting the 14-3-3 protein interface

Dario Valenti, João Filipe Neves, François-Xavier Cantrelle, Stanimira Hristeva, Domenico Lentini Santo, Tomáš Obšil, Xavier Hanoulle, Laura M. Levy, Dimitrios Tzalis, Isabelle Landrieu, Christian Ottmann

 

Med. Chem. Commun., Jul 2019, DOI:10.1039/C9MD00215D

Abstract:

Protein–protein interactions (PPIs) are at the core of regulation mechanisms in biological systems and consequently became an attractive target for therapeutic intervention. PPIs involving the adapter protein 14-3-3 are representative examples given the broad range of partner proteins forming a complex with one of its seven human isoforms. Given the challenges represented by the nature of these interactions, fragment-based approaches offer a valid alternative for the development of PPI modulators. After having assembled a fragment set tailored on PPIs’ modulation, we started a screening campaign on the sigma isoform of 14-3-3 adapter proteins. Through the use of both mono- and bi-dimensional nuclear magnetic resonance spectroscopy measurements, coupled with differential scanning fluorimetry, three fragment hits were identified. These molecules bind the protein at two different regions distant from the usual binding groove highlighting new possibilities for selective modulation of 14-3-3 complexes.

Want to know more about this publication?
Contact our scientists

Medicinal chemistry

Drug Discovery

Taros’ international and multidisciplinary team has more than 180 years of pharmaceutical R&D experience. Collectively as a team, we worked on more than 120 biomolecular…

custom chemical services

Custom Synthesis

We support our customers by providing first kg quantities of fine and specialty chemicals, cost reduction of existing syntheses, streamlining chemical processes considering…

Looks interesting?

As a leading CRO in Europe, Taros provides comprehensive drug discovery chemistry services for large Pharma and Biotech corporations as well as for Research Institutes and Academia

Our experienced chemists practice a pragmatic culture and customer-centric approach in order to exceed project expectations and, despite challenges, bridge very narrow timelines. They are trained to consider economic, safety and ecological boundaries and conditions laid out for all stages of the project.
Scroll to Top