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Volume 7, Issue 1 (Suppl) J Biotechnol Biomater
ISSN: 2155-952X JBTBM, an open access journal
March 20-21, 2017 Rome, Italy
&
15th World Congress on
2nd International Conference on
Biotechnology And Biotech Industries Meet
Enzymology and Molecular Biology
Enzymology & Mol. Biology 2017
Biotechnology Congress 2017
March 20-21, 2017
Julie Alexandre et al., J Biotechnol Biomater 2017, 7:1(Suppl)
Novel human indoleamine 2,3-dioxygenase inhibitors form a long-lived complex with the enzyme
Julie Alexandre, Michael Swan, Mike Latchem, Dean Boyall, John Pollard, Stuart Hughes and James Westcott
Vertex Pharmaceuticals Ltd., UK
Human indoleamine 2,3-dioxygenase 1 (IDO) catalyzes the conversion of L-tryptophan (L-Trp) to N-formylkynurenine through
a heme and O2-dependent oxidation process. IDO is recognized as a central regulator of immune responses in a broad variety of
physiological and pathological settings and is thus considered an attractive therapeutic target. In search of novel IDO inhibitors, we
identified 4-amino-1,2,3-triazoles. Using crystallographic, biochemical and spectroscopic techniques we have fully characterized a
representative molecule of this molecular series (VIDOi1) and shown that: VIDOi1 is non-competitive for D-Trp; VIDOi1 interacts
with the IDO heme iron VIDOi1 binds to both the ferric and the ferrous form of the enzyme; VIDOi1establishes a slow complex with
the ferrous form of IDO; and the VIDOi1-IDO complex is long-lived. The generation of this tight binding complex between IDO and
the 4-amino -1,2,3-triazoles leads to exceptional potencies of this molecule series in a cellular context.
Biography
Julie Alexandre is specialized in Kinetics at the Vertex Pharmaceuticals Europe Ltd., (Abingdon, UK). She holds a PhD in Biochemistry from the University of
Edinburgh (Scotland, UK) and undertook Post-doctoral Research in Enzymology at the Pierre-and-Marie-Curie University (Paris, France). She has been working
at Vertex since 9 years and has contributed in many internal drug discovery efforts in oncology, targeting kinases, proteases and redox enzymes, through
characterization of enzymes substrates and inhibitors kinetics and mode of action.