Project

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

Duration
01 October 2010 → 30 September 2012
Funding
Regional and community funding: Special Research Fund
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
maspit target identification methotrexate
 
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 promotor.

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.