De Clercq, Dries

Lievens, Sam

Risseeuw, Martijn

Tavernier, Jan

Van Calenbergh, Serge

English

Ghent University Academic Bibliography

Syntheses of Methotrexate-hybrid compounds for target profiling of small molecules with MASPIT  Dries De Clercq1, Martijn Risseeuw1, Sam Lievens2, Jan Tavernier2 and Serge Van Calenbergh1  1 Laboratory for Medicinal Chemistry (FFW), Ghent University, Harelbekestraat 72, B-9000 Gent, Belgium 2 Cytokine Receptor Lab, Department of Medical Protein Research, VIB, Gent (Belgium) and Department of Bio-chemistry, Ghent University, Gent (Belgium)  To understand the molecular basis of the mode of action of organic small molecules, it is essential to identify their cellular target proteins. Mammalian small molecule-protein interaction trap (MASPIT[1]) provides a new tool for target-elucidation of small molecules, based on the cytokine-receptor-associated JAK-STAT-signal transduction system.    We set out to synthesize alkyne-functionalized analogues of blockbuster drugs (simvastatin, propranolol and tamoxifen) and the small molecule reversine, paying close attention to SAR. These analogues were conjugated with an azide containing MTX-reagent via the Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition (CLICK chemistry). The resulting MTX-conjugates are currently being evaluated in the MASPIT assay.  [1] Caligiuri, M.et al. Chem. Biol. 2006, 13, 711–722. 

Syntheses of methotrexate-hybrid compounds for target profiling of small molecules with MASPIT

https://biblio.ugent.be/publication/3198196/file/3198264

Syntheses of methotrexate-hybrid compounds for target profiling of small molecules with MASPIT

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Ghent University Academic Bibliography