Mehellou, Youcef - University of Birmingham

个人简介

Youcef took up his position as a Lecturer in Medicinal Chemistry on the 1st March 2013. Youcef obtained his Ph.D. from the Welsh School of Pharmacy, Cardiff University. Youcef’s postgraduate research was carried out in the laboratory of Prof. Christopher McGuigan. The project was on the design, synthesis and development of nucleoside analogues and their phosphate prodrugs (Phosphoramidates) as potential antiviral and anticancer therapies. During this work, Youcef synthesised a large number of nucleoside analogues and their phosphoramidate derivatives and explored their potential as antiviral and anticancer compounds in collaboration with Prof. Jan Balzarini. Youcef used molecular modelling as well as NMR studies to investigate the differences in biological activities seen with some of the nucleoside analogues phosphoramidates. This was followed by a Postdoc with Prof. Sidney M. Hecht at the Biodesign Institute, Arizona State University, USA. Youcef’s work then was on the development of chemical strategies that allow the incorporation of unnatural amino acids into proteins. This involved the synthesis of unnatural amino acids and ligating them to synthetic dinucleotides. In late 2010, Youcef took a position as an MRC Career Development Fellow with Prof. Dario R. Alessi (FRS) at the MRC Protein Phosphorylation and Ubiquitylation Unit (MRC PPU), University of Dundee. While in this position, Youcef’s work was concerned with the regulation of the catalytic activity of kinases, particularly SPAK, OSR1 and MSTs, by the scaffolding protein MO25. Youcef solved the crystal structure of the kinase MST3 in complex with MO25, which shed some light on the activation of kinases by MO25. Youcef also worked on developing high throughput screening assays for identifying small molecules that inhibit various components of the WNK signalling pathway of which SPAK and OSR1 kinases are part of. Youcef obtained his first degree (Pharmacy) from King’s College London.

研究领域

Youcef’s teaching and research interests are focused on Biological and Medicinal Chemistry

近期论文

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Nguyen, H.V., Sallustrau, A., Balzarini, J., Bedford, M.R., Eden, J.C., Georgousi, N., Hodges, N.J., Kedge J., Mehellou, Y., Tselepis, C., Tucker, J.H. Organometallic nucleoside analogues with ferrocenyl linker groups: synthesis and cancer cell line studies. J Med Chem. 2014, 57, 13, 5817-5822. Ohta, A., Schumacher, F.R., Mehellou, Y., Johnson, C., Knebel, A., Macartney, T.J., Wood, N.T., Alessi, D.R., Kurz, T, 2013, The CUL3-KLHL3 E3 ligase complex mutated in Gordon's hypertension syndrome interacts with and ubiquitylates WNK isoforms; disease-causing mutations in KLHL3 and WNK4 disrupt interaction. Biochem J. 2013, 451, 111-122 Mehellou, Y., Alessi, D.R., Macartney, T.J., Szklarz, M., Knapp, S., Elkins, J.M., Structural insights into the activation of MST3 by MO25, Biochem. Biophys. Res. Commun. 2013, 431, 604-609. Chen, S., Fahmi, N.E., Nangreave, R.C., Mehellou, Y., Hecht, S.M., Synthesis of pdCpAs and transfer RNAs activated with thiothreonine and derivatives. Bioorg. Med. Chem. 2012, 20, 2679-2689. Thastrup, J.O., Rafiqi, F.H., Vitari, A.C., Pozo-Guisado, E., Deak, M., Mehellou, Y., Alessi, D.R., SPAK/OSR1 regulate NKCC1 and WNK activity: analysis of WNK isoform interactions and activation by T-loop trans-autophosphorylation, Biochem. J. 2012, 441, 325-337. Filippi, B.M., de los Heros, P., Mehellou, Y., Navratilova, I., Gourlay, R., Deak, M., Plater, L., Toth, R., Zeqiraj, E., Alessi, D.R., MO25 is a master regulator of SPAK/OSR1 and MST3/MST4/YSK1 protein kinases. EMBO J. 2011, 30, 1730-1741. Mehellou, Y. Phosphoramidate prodrugs deliver with potency against hepatitis?C virus. ChemMedChem. 2010, 5, 1841-1842. Mehellou, Y., Valente, R., Mottram, H., Walsby, E., Mills, K.I., Balzarini, J., McGuigan, C., Phosphoramidates of 2'-beta-D-arabinouridine (AraU) as phosphate prodrugs; design, synthesis, in vitro activity and metabolism. Bioorg. Med. Chem. 2010, 18, 2439-2446. Mehellou, Y., Balzarini, J., McGuigan, C., The design, synthesis and antiviral evaluation of a series of 5-trimethylsilyl-1-beta-D-(arabinofuranosyl)uracil phosphoramidate ProTides, Antivir. Chem. Chemother. 2010, 20, 153-160. Mehellou, Y., Balzarini, J., McGuigan, C., An investigation into the anti-HIV activity of 2',3'-didehydro-2',3'-dideoxyuridine (d4U) and 2',3'-dideoxyuridine (ddU) phosphoramidate 'ProTide' derivatives. Org. Biomol. Chem. 2009, 7, 2548-53.