ml500385d_si_001.pdf (2.61 MB)
N1‑Fluoroalkyltryptophan Analogues: Synthesis and in vitro Study as Potential Substrates for Indoleamine 2,3-Dioxygenase
journal contribution
posted on 2015-03-12, 00:00 authored by Jean Henrottin, Astrid Zervosen, Christian Lemaire, Frédéric Sapunaric, Sophie Laurent, Benoit Van den
Eynde, Serge Goldman, Alain Plenevaux, André LuxenIndoleamine
2,3-dioxygenase (hIDO) is an enzyme that catalyzes
the oxidative cleavage of the indole ring of l-tryptophan
through the kynurenine pathway, thereby exerting immunosuppressive
properties in inflammatory and tumoral tissues. The syntheses of 1-(2-fluoroethyl)-tryptophan
(1-FETrp) and 1-((1-(2-fluoroethyl)-1H-1,2,3-triazol-4-yl)methyl)-tryptophan,
two N1-fluoroalkylated tryptophan derivatives,
are described here. In vitro enzymatic assays with
these two new potential substrates of hIDO show that 1-FETrp is a
good and specific substrate of hIDO. Therefore, its radioactive isotopomer,
1-[18F]FETrp, should be a molecule of choice to visualize
tumoral and inflammatory tissues and/or to validate new potential
inhibitors.