Project

Development of methotrexate conjugates for the identification of new intracellular targets via the Maspit technology

Duration
01 January 2010 → 31 December 2015
Funding
Research Foundation - Flanders (FWO)
Research disciplines
  • Natural sciences
    • Organic chemistry
  • Medical and health sciences
    • Biomarker discovery and evaluation
    • Drug discovery and development
    • Medicinal products
    • Pharmaceutics
    • Pharmacognosy and phytochemistry
    • Pharmacology
    • Pharmacotherapy
    • Toxicology and toxinology
    • Other pharmaceutical sciences
Keywords
methotrexate conugates maspit target identification
 
Project description

This project aims to apply a mammalian small molecule protein interaction trap (MASPIT) to discover new intracellular therapeutic targets. In MASPIT a dihydrofolate reductase fusion protein is used to anchor the methotrexate (MTX) part of a MTX-bait conjugate, which permits to present the bait 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.The goal of this project is to devise a suitable strategy for the synthesis of MTX-bait conjugates to identify hitherto unknown targets of therapeutically interesting small molecules.