Chemistry

Ali Tavassoli

Primary position:
Reader in Chemical Biology

Background

The University of Southampton

Ali Tavassoli's Publications and Citation Metrics

Tavassoli lab website

Ali is a Reader in chemical biology, jointly appointed to Chemistry (Faculty of Natural and Environmental Sciences) and Cancer Sciences (Faculty of Medicine).

Ali Currently leads an interdisciplinary team of scientists whose efforts are focused on the development of novel chemical tools that enable new insight into the role of protein-protein interactions in cell biology, and as the starting point for new therapeutics.

Ali has published over 40 papers that have been cited over 500 times, including research publications as corresponding author in leading journals such as the Proceedings of the Natlional Academy of Sciences, Journal of the American Chemical Society, Angewandte Chemie, and Chemical Science.

Over the past 5 years, Ali has raised over £2.8M of research funding as PI and £700K as CoI (from grants totaling £5.2M). This has included research grants from the UK Research Councils (EPSRC, BBSRC and MRC), UK Charities (Cancer Research UK, Breast Cancer Campaign, The Kerkut Trust, The Wessex Medical Research Trust) and several pharmaceutical companies (AstraZeneca, GlaxoSmithKline, Pfizer and C4X drug discovery).

Ali is currently Chair of the RSC's "Chemical Biology and Bioorganic Group", and an elected member of the RSC's "Chemistry and Biology Interface Division" council.

Ali has won a number of awards during his career, including the European Association for Chemical and Molecular Sciences' medal for European Young Chemist (in 2008). 

Dr Ali Tavassoli's photo

Publications

The University of Southampton's electronic library (e-prints)

Key Publications

Birts, Charles N., Sanzone, A. Pia, El-Sagheer, Afaf H., Blaydes, Jeremy P., Brown, Tom and Tavassoli, Ali (2014) Transcription of click-linked DNA in human cells. Angewandte Chemie International Edition in English, 53, (9), 2362-2365. (doi:10.1002/anie.201308691). (PMID:24452865).
Miranda, Elena, Nordgren, Ida, Male, Abigail, Lawrence, Charlotte, Hoakwie, Franciane, Cuda, F., Court, William, Fox, Keith R., Townsend, Paul, Packham, Graham K., Eccles, Suzanne A. and Tavassoli, Ali (2013) A cyclic peptide inhibitor of HIF-1 heterodimerization that inhibits hypoxia signaling in cancer cells. Journal of the American Chemical Society, 135, (28), 10418-10425. (doi:10.1021/ja402993u). (PMID:23796364).
Birts, Charles N., Nijjar, Sharandip K., Mardle, Charlotte A., Hoakwie, Franciane, Duriez, Patrick J., Blaydes, Jeremy P. and Tavassoli, Ali (2013) A cyclic peptide inhibitor of C-terminal binding protein dimerization links metabolism with mitotic fidelity in breast cancer cells. Chemical Science, 4, (8), 3046-3057. (doi:10.1039/c3sc50481f).
El-Sagheer, Afaf H., Sanzone, A Pia, Gao, Rachel, Tavassoli, Ali and Brown, Tom (2011) Biocompatible artificial DNA linker that is read through by DNA polymerases and is functional in Escherichia coli. Proceedings of the National Academy of Sciences, 108, (28), 11338-11343. (doi:10.1073/pnas.1101519108). (PMID:21709264).

Article

Bartlett, Nathan, Gross, Leona, Péron, Florent, Asby, Daniel J., Selby, Matthew D., Tavassoli, Ali and Linclau, Bruno (2014) Stereocontrol by quaternary centres: a stereoselective synthesis of (−)-luminacin D. Chemistry - A European Journal, 20, (12), 3306-3310. (doi:10.1002/chem.201304776). (PMID:24519660).
Nordgren, Ida Karin and Tavassoli, Ali (2014) A bidirectional fluorescent two-hybrid system for monitoring protein–protein interactions. Molecular BioSystems, 10, (3), 485-490. (doi:10.1039/c3mb70438f). (PMID:24382456).
Andrews, Allison-Lynn, Nordgren, Ida Karin, Campbell-Harding, Gemma, Holloway, John W., Holgate, Stephen T., Davies, Donna E. and Tavassoli, Ali (2013) The association of the cytoplasmic domains of interleukin 4 receptor alpha and interleukin 13 receptor alpha 2 regulates interleukin 4 signaling. Molecular BioSystems, 9, (12), 3009-3014. (doi:10.1039/C3MB70298G). (PMID:24056919).
Dankar, S.K., Miranda, Elena, Forbes, N.E., Pelchat, M., Tavassoli, Ali, Selman, M., Ping, J., Jia, J. and Brown, E.G. (2013) Influenza A/Hong Kong/156/1997(H5N1) virus NS1 gene mutations F103L and M106I both increase IFN antagonism, virulence and cytoplasmic localization but differ in binding to RIG-I and CPSF30. Virology Journal, 10, (243) (doi:10.1186/1743-422X-10-243). (PMID:23886034).
Tavassoli, Ali, Brown, Tom, El-Sagheer, Afaf H. and Sanzone, A. Pia (2012) Assessing the biocompatibility of click-linked DNA in Escherichia coli. Nucleic Acids Research, 40, (20), 10567-10575. (doi:10.1093/nar/gks756). (PMID:22904087).
Spurr, Ian B., Birts, Charles N., Cuda, Francesco, Benkovic, Stephen J., Blaydes, Jeremy P. and Tavassoli, Ali (2012) Targeting tumour proliferation with a small-molecule inhibitor of AICAR Transformylase Homodimerization. ChemBioChem, 13, (11), 1628-1634. (doi:10.1002/cbic.201200279). (PMID:22764122).
Miranda, Elena, Forafonov, Fedor and Tavassoli, Ali (2011) Deciphering interactions used by the influenza virus NS1 protein to silence the host antiviral sensor protein RIG-I using a bacterial reverse two-hybrid system. Molecular BioSystems, 7, (4), 1042-1045. (doi:10.1039/C0MB00318B). (PMID:21264376).
Tavassoli, Ali (2010) Synthetic biology. Organic & Biomolecular Chemistry, 8, 24-28. (doi:10.1039/b913300n).
Andrews, Allison-Lynn , Nordgren, Ida Karin, Kirby, Isabelle , Holloway, John W., Holgate, Stephen T., Davies, Donna E. and Tavassoli, Ali (2009) Cytoplasmic tail of IL-13Rα2 regulates IL-4 signal transduction. Biochemical Society Transactions, 37, 873-876. (doi:10.1042/BST0370873).
Tavassoli, Ali , Lu, Quan , Gam, Jongsik, Pans, Hui, Benkovic, Stephen J. and Cohen, Stanley N. (2008) Inhibition of HIV budding by a genetically selected cyclic peptide targeting the Gag−TSG101 interaction. ACS Chemical Biology, 3, (12), 757-764. (doi:10.1021/cb800193n). (PMID:19053244).
Naumann, Todd A., Tavassoli, Ali and Benkovic, Stephen J. (2008) Genetic selection of cyclic peptide dam methyltransferase inhibitors. ChemBioChem, 9, (2), 194-197. (doi:10.1002/cbic.200700561).
Sweeney, J.B., Tavassoli, Ali and Workman, James A. (2006) Asymmetric ammonium ylid rearrangements: the effect of nitrogen asymmetry. Tetrahedron, 62, (49), 11506-11512. (doi:10.1016/j.tet.2006.06.043).
Cheng, H., Hwang, I., Chong, Y.H., Tavassoli, A., Webb, M.E., Zhang, Y., Wilson, I.A., Benkovic, S.J. and Boger, D.L. (2005) Synthesis and biological evaluation of N-{4-[5-(2,4-diamino-6-oxo-1,6-dihydropyrimidin-5-yl)-2-(2,2,2-trifluoro acetyl)pentyl)benzoyl}-L-glutamic acid as a potential inhibitor of GAR Tfase and the de novo purine biosynthetic pathway. Bioorganic & Medicinal Chemistry, 13, (10), 3593-3599. (doi:10.1016/j.bmc.2004.11.049).
Cheng, Heng, Hwang, Inkyu, Chong, Youhoon, Tavassoli, Ali, Webb, Michael E., Zhang, Yan, Wilson, Ian A., Benkovic, Stephen J. and Boger, Dale L. (2005) Synthesis and biological evaluation of N-[4-[5-(2,4-diamino-6-oxo-1,6-dihydropyrimidin-5-yl)-2-(2,2,2-trifluoroac etyl)pentyl]benzoyl]-L-glutamic acid as a potential inhibitor of GAR Tfase and the de novo purine biosynthetic pathway. Bioorganic & Medicinal Chemistry, 13, (10), 3593-3599. (doi:10.1016/j.bmc.2004.11.049).
Cheng, Heng, Chong, Youhoon, Hwang, Inkyu, Tavassoli, Ali, Zhang, Yan, Wilson, Ian A., Benkovic, Stephen J. and Boger, Dale L. (2005) Design, synthesis, and biological evaluation of 10-methanesulfonyl-DDACTHF, 10-methanesulfonyl-5-DACTHF, and 10-methylthio-DDACTHF as potent inhibitors of GAR Tfase and the de novo purine biosynthetic pathway. Bioorganic & Medicinal Chemistry, 13, (10), 3577-3585. (doi:10.1016/j.bmc.2004.12.004).
Tavassoli, Ali and Benkovic, Stephen J. (2005) Genetically selected cyclic-peptide inhibitors of AICAR transformylase homodimerization. Angewandte Chemie International Edition, 44, (18), 2760-2763. (doi:10.1002/anie.200500417).
Chong, Youhoon, Hwang, Inkyu, Tavassoli, Ali, Zhang, Yan, Wilson, Ian A., Benkovic, Stephen J. and Boger, Dale L. (2005) Synthesis and biological evaluation of alpha- and gamma-carboxamide derivatives of 10-CF3CO-DDACTHF. Bioorganic & Medicinal Chemistry, 13, (10), 3587-3592. (doi:10.1016/j.bmc.2004.11.050).
Marsilje, T.H., Hedrick, M.P., Desharnais, J., Capps, K., Tavassoli, A., Zhang, Y., Wilson, I.A., Benkovic, S.J. and Boger, D.L. (2003) 10-(2-benzoxazolcarbonyl)-5,10-dideaza-acyclic-5,6,7,8-tetrahydrofolic acid: A potential inhibitor of GAR transformylase and AICAR transformylase. Bioorganic & Medicinal Chemistry, 11, (20), 4503-4509. (doi:10.1016/S0968-0896(03)00457-7).
Marsilje, Thomas H., Hedrick, Michael P., Desharnais, Joel, Tavassoli, Ali, Zhang, Yan, Wilson, Ian A., Benkovic, Stephen J. and Boger, Dale L. (2003) Design, synthesis, and biological evaluation of simplified alpha-keto heterocycle, trifluoromethyl ketone, and formyl substituted folate analogues as potential inhibitors of GAR transformylase and AICAR transformylase. Bioorganic & Medicinal Chemistry, 11, (20), 4487-4501. (doi:10.1016/S0968-0896(03)00456-5).
Zhang, Y., Desharnais, J., Marsilje, T.H., Li, C.L., Hedrick, M.P., Gooljarsingh, L.T., Tavassoli, A., Benkovic, S.J., Olson, A.J., Boger, D.L. and Wilson, I.A. (2003) Rational design, synthesis, evaluation, and crystal structure of a potent inhibitor of human GAR tfase: 10-(trifluoroacetyl)-5,10-dideazaacyclic-5,6,7,8-tetrahydrofolic acid. Biochemistry, 42, (20), 6043-6056. (doi:10.1021/bi034219c).
Desharnais, Joel, Hwang, Inkyu, Zhang, Yan, Tavassoli, Ali, Baboval, Justin, Benkovic, Stephen J., Wilson, Ian A. and Boger, Dale L. (2003) Design, synthesis and biological evaluation of 10-CF3CO-DDACTHF analogues and derivatives as inhibitors of GAR Tfase and the de novo purine biosynthetic pathway. Bioorganic & Medicinal Chemistry, 11, (20), 4511-4521. (doi:10.1016/S0968-0896(03)00458-9).
Marsilje, Thomas H., Hedrick, Michael P., Desharnais, Joel, Capps, Kevin, Tavassoli, Ali, Zhang, Yan, Wilson, Ian A., Benkovic, Stephen J. and Boger, Dale L. (2003) 10-(2-benzoxazolcarbonyl)-5,10-dideaza-acyclic-5,6,7,8-tetrahydrofolic acid: a potential inhibitor of GAR transformylase and AICAR transformylase. Bioorganic & Medicinal Chemistry, 11, (20), 4503-4509. (doi:10.1016/S0968-0896(03)00457-7).
Zhang, Yan, Desharnais, Joel, Marsilje, Thomas H., Li, Chenglong, Hedrick, Michael P., Gooljarsingh, Lata T., Tavassoli, Ali, Benkovic, Stephen J., Olson, Arthur J., Boger, Dale L. and Wilson, Ian A. (2003) Rational design, synthesis, evaluation, and crystal structure of a potent inhibitor of human GAR Tfase: 10-(trifluoroacetyl)-5,10-dideazaacyclic-5,6,7,8-tetrahydrofolic acid. Biochemistry, 42, (20), 6043-6056. (doi:10.1021/bi034219c).
Marsilje, T.H., Labroli, M.A., Hedrick, M.P., Jin, Q., Desharnais, J., Baker, S.J., Gooljarsingh, L.T., Ramcharan, J., Tavassoli, A., Zhang, Y., Wilson, I.A., Beardsley, G.P., Benkovic, S.J. and Boger, D.L. (2002) 10-formyl-5,10-dideaza-acyclic-5,6,7,8-tetrahydrofolic acid (10-formyl-DDACTHF) a potent cytotoxic agent acting by selective inhibition of human GAR Tfase and the de novo purine biosynthetic pathway. Bioorganic & Medicinal Chemistry, 10, (8), 2739-2749. (doi:10.1016/S0968-0896(02)00102-5).
Marsilje, Thomas H., Labroli, Marc A., Hedrick, Michael P., Jin, Qing, Desharnais, Joel, Baker, Stephen J., Gooljarsingh, Lata T., Ramcharan, Joseph, Tavassoli, Ali, Zhang, Yan, Wilson, Ian A., Beardsley, G. Peter, Benkovic, Stephen J. and Boger, Dale L. (2002) 10-Formyl-5,10-dideaza-acyclic-5,6,7,8-tetrahydrofolic acid (10-formyl-DDACTHF): a potent cytotoxic agent acting by selective inhibition of human GAR Tfase and the de novo purine biosynthetic pathway. Bioorganic & Medicinal Chemistry, 10, (8), 2739-2749. (doi:10.1016/S0968-0896(02)00102-5).
Sweeney, J.B., Tavassoli, Ali and Workman, J.A. (2002) 2,3-sigmatropic rearrangements of ammonium ylids. Abstracts of Papers of the American Chemical Society, 224, U215.
Sweeney, J.B., Tavassoli, Ali, Carter, Neil B. and Hayes, Jerome F. (2002) [2,3]-Sigmatropic rearrangements of didehydropiperidinium ylids. Tetrahedron, 58, (51), 10113-10126. (doi:10.1016/S0040-4020(02)01397-2).
George, Trevor, Mabon, Ross, Sweeney, Gemma, Sweeney, J.B. and Tavassoli, Ali (2000) Alcohols, ethers and phenols. Journal of the Chemical Society, Perkin Transactions 1, (16), 2529-2574. (doi:10.1039/a808133f).
Hyett, David J., Sweeney, J.B., Tavassoli, Ali and Hayes, Jerome F. (1997) Factors affecting the [3,2]-sigmatropic rearrangements of didehydropiperidinium ylids. Tetrahedron Letters, 38, (47), 8283-8286. (doi:10.1016/S0040-4039(97)10168-X).

Book Section

Forafonov, Fedor, Miranda, Elena, Nordgren, Ida Karin and Tavassoli, Ali (2010) Targeting disease with small molecule inhibitors of protein–protein interactions. In, Pignataro, Bruno (ed.) Ideas in Chemistry and Molecular Sciences. Weinheim, DE, Wiley-VCH, 215-238. (Where Chemistry Meets Life).
 

Research

Research Interests

The main focus of the Tavassoli lab has been the establishment and utilization of a genetically encoded high-throughput screening platform for the identification of protein-protein interaction inhibitors. our goal is the development of compounds capable of disrupting the association and assembly of protein complexes. A key area of interest for the lab is uncovering compounds that disrupt metabolite-sensing transcription factors. The compounds uncovered in our lab serve as valuable tools that allow better understanding of the link between tumour metabolism and the altered gene expression of cancer cells. These compounds also form the starting point for the development of therapeutic compounds that target key protein-protein interactions in disease. Our research group is focused on training scientists at the chemistry-biology interface, and using these interdisciplinary skills to help understand the fundamentals of cell biology and to develop new therapeutic agents.

Some of the projects currently underway in the lab are highlighted below.

The first specific inhibitor of HIF-1α/HIF-1β protein-protein interaction

Miranda E, et al., Journal of the American Chemical Society, 2013, 135 (28), 10418-10425.

HIF-1 is the cellular sensor of oxygen, and a key protein in the adaptation and survival of cancer cells in the hypoxic tumour microenvironment. We have recently reported the first specific inhibitor of HIF1α/HIF-1β dimerization. The inhibitor was identified using our bacterial high-throughput screening platform, and was extensively characterized in vitro and in cells, and shown to inhibit hypoxia-response signaling in cells. We also demonstrated that the compound does not disrupt the dimerization of HIF-2α/HIF-1β in vitro and in cells.

This work has generated significant media interest, including the CRUK blog.

This work is funded by Cancer Research UK

The first example of a non-natural, biocompatible DNA-backbone linker (with Prof. Tom Brown)

Birts C.N. et al., Angewandte Chemie, 2014, available online ahead of print.

Sanzone A.P. et al., Nucleic Acids research, 2012, 40 (20), 10567-10575.

El-Sagheer A.H. et al., Proceedings of the National Academy of Science, 2011, 108 (28), 11338-11343.

Current DNA synthesis methods do not allow the preparation of epigenetically modified DNA fragments larger than ~200 bases (methods such as PCR use enzymes that can not read epigenetic information, and so any epigenetic information incorporated at the oligonucleotide synthesis stage will be erased in the amplified, assembled DNA). We are therefore seeking to establish a chemical method for DNA ligation that would allow assembly of synthetic oligonucleotides by a purely chemical method. This would allow the synthesis of large oligonucleotides (genes and genomes) that contain epigenetic information, and provide a significant tool for the study of epigenetics.

A key requirement for the above is the biocompatibility of the resulting non-natural DNA linker in living systems. We have assesses the suitability of click-linked DNA for this purpose; modified bases were incorporated at the appropriate termini of oligonucleotides, and linked by click chemistry. We have recently shown that the resulting non-natural triazole linked (replacing the phosphodiester normally present in DNA) is fully biocompatible in E. coli and mammalian cells.

 This work is funded by the BBSRC and EPSRC.

The first inhibitor of CtBP homodimerization (with Dr. Jeremy Blaydes)

Birts C.N. et al., Chemical Science, 2013, 4 (8), 3046-3057.

C-termina binding proteins are transcriptional regulators that dimerize in response to increased NADH levels, and modulate the gene expression. We used our high-throughput screening platform to identify cyclic peptide inhibitors of CtBP dimerization, and used these sompounds to show metabolic regulation of cell cycle fidelity in cancer cells. Our paper was featured on the cover of the journal Chemical Science.

This work is funded by Cancer Research UK and Breast Cancer Campaign.

Primary research group:  

Research projects

Tavassoli: Cancer Research

Tavassoli: HIV Research

Tavassoli: Synthetic Biology

Contact

Dr Ali Tavassoli
Chemistry
University of Southampton
Highfield
Southampton
SO17 1BJ

Room Number: 30/4049

Telephone: (023) 8059 2395
Email: A.Tavassoli@soton.ac.uk