MTX conjugates for identification of new targets using MASPIT


The number of therapeutic targets that the modern pharmacopoeia acts on is surprisingly small (ca. 500) and only a small fraction of the recently approved drugs interferes with new target families.

This project aims to explore MASPIT, a 3-hybrid variant developed in the Cytokine Receptor Laboratory (CRL), for the identification of novel intracellular therapeutic targets.

In MASPIT a dihydrofolate reductase fusion protein forms a high affinity binding site for the methotrexate (MTX) part of a MTX–“bait” conjugate, allowing to present a “bait” compound to the intracellular environment. A “bait”–“prey” interaction activates the JAK2-STAT3 signalization and can be easily detected via a reporter protein (e.g., luciferase), whose expression is controlled by a STAT3-responsive promoter.



Overview of the MASPIT system

Our role in this project involves the synthesis of versatile MTX building blocks which will be used for the construction of MTX–“bait” conjugates of a series of therapeutically interesting small molecules.

Identification of new intracellular targets may feed new target-based drug discovery projects.

ResearcherDr. Martijn Risseeuw

Collaborators: Prof. Jan Tavernier, Dr. Sam Lievens (Cytokine Receptor Laboratory, UGent)