Howell, Lesley - University of East Anglia

个人简介

Lesley graduated with an MChem (First Class Honours) in Chemistry with a Year in Industry from the University of York in 2006, having spent a year working as an Analytical Scientist at GlaxoSmithKline in Stevenage. She then moved to the University of East Anglia to carry out a PhD in Medicinal Chemistry under the supervision of Professor Mark Searcey. Her thesis was titled “Design, Synthesis and Biological Evaluation of 9-Aminoacridines that Target the Holliday Junction”. After the successful completion of her PhD in 2009 she took up a position as a Senior Demonstrator in Pharmacy in the School of Pharmacy at UEA. After a little over two years in the position she was appointed to the position of Lecturer in Medicinal Chemistry in January 2012.

研究领域

Lesley’s research interests include identifying small therapeutically interesting molecules that target DNA and protein-protein interactions (PPIs), often using the structures of natural products as a starting point. The group uses a mixture of both solid and solution phase chemistry and PPIs currently under investigation include p53/MDM2, p53/MDMX and Mcl-1. The overarching goal is to develop analogues with clinical potential. We are currently focussed on targeting PPIs involved in cancer as well as natural products that can potentially be developed into new antibacterial agents.

近期论文

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Beekman, A. M., O'Connell, M. A., Howell, L. A.(2016)Identification of Small-Molecule Inhibitors of the Antiapoptotic Protein Myeloid Cell Leukaemia-1 (Mcl-1)in ChemMedChem11.pp. 840–844 Full Text(Letter)Howell, L., Beekman, A.(2016)Small molecule and peptide inhibitors of the pro-survival protein Mcl-1in ChemMedChem11.pp. 802–813 Full Text UEA Repository(Article) Angulo, J., Goffin, S., Gandhi, D., Searcey, M., Howell, L.(2016)Unveiling the "Three Finger Pharmacophore" required for p53-MDM2 Inhibition by Saturation Transfer Difference NMR Initial Growth Rates Approachin Chemistry - A European Journal22.pp. 5858-5862 Full Text UEA Repository(Article) Austin, M. J., Hearnshaw, S. J., Mitchenall, L. A., McDermott, P. J., Howell, L. A., Maxwell, A., Searcey, M.(2016)A natural product inspired fragment-based approach towards the development of novel anti-bacterial agentsin MedChemComm7.pp. 1387-1391 Full Text UEA Repository(Article) Busnelli, M., Kleinau, G., Muttenthaler, M., Stoev, S., Manning, M., Bibic, L., Howell, L. A., McCormick, P. J., Di Lascio, S., Braida, D., Sala, M., Rovati, G. E., Bellini, T., Chini, B.(2016)Design and characterization of superpotent bivalent ligands targeting oxytocin receptor dimers via a channel-like structurein Journal of Medicinal Chemistry59.pp. 7152–7166 Full Text UEA Repository(Article) Navarro, G., Quiroz, C., Moreno-Delgado, D., Sierakowiak, A., McDowell, K., Moreno, E., Rea, W., Cai, N., Aguinaga, D., Howell, L. A., Hausch, F., Cortés, A., Mallol, J., Casadó, V., Lluís, C., Canela, E. I., Ferré, S., McCormick, P. J.(2015)Orexin-Corticotropin-Releasing Factor Receptor Heteromers in the Ventral Tegmental Area as Targets for Cocainein The Journal of Neuroscience35.pp. 6639-6653 Full Text UEA Repository(Article) Cominetti, M., Goffin, S., Raffel, E., Turner, K., Ramoutar, J., O'Connell, M., Howell, L., Searcey, M.(2015)Identification of a new p53/MDM2 inhibitor motif inspired by studies of chlorofusinin Bioorganic & Medicinal Chemistry Letters25.pp. 4878-4880 Full Text UEA Repository(Article) Viñals, X., Moreno, E., Lanfumey, L., Cordomí, A., Pastor, A., de La Torre, R., Gasperini, P., Navarro, G., Howell, L., Pardo, L., Lluís, C., Canela, E. I., McCormick, P. J., Maldonado, R., Robledo, P.(2015)Cognitive Impairment Induced by Delta9-tetrahydrocannabinol Occurs through Heteromers between Cannabinoid CB1 and Serotonin 5-HT2A Receptorsin PLoS Biology13. Full Text UEA Repository(Article) Stephenson, M., Howell, L., O'Connell, M., Fox, K. R., Adcock, C., Kingston, J., Sheldrake, H., Pors, K., Collingwood, S., Searcey, M.(2015)Solid-phase synthesis of duocarmycin analogues and the effect of C-terminal substitution on biological activityin The Journal of Organic Chemistry80.pp. 9454–9467 Full Text UEA Repository(Article) Waller, Z. A. E., Howell, L. A., Macdonald, C. J., O'Connell, M. A., Searcey, M.(2014)Identification and characterisation of a G-quadruplex forming sequence in the promoter region of nuclear factor (erythroid-derived 2)-like 2 (Nrf2)in Biochemical and Biophysical Research Communications447.pp. 128-32 Full Text UEA Repository(Article) Rackham, B. D., Howell, L. A., Round, A. N., Searcey, M.(2013)Non-covalent duplex to duplex crosslinking of DNA in solution revealed by single molecule force spectroscopyin Organic & Biomolecular Chemistry11.pp. 8340-8347 Full Text UEA Repository(Article) Marin, M., Rackham, B. D., Round, A. N., Howell, L. A., Russell, D. A., Searcey, M.(2013)A rapid screen for molecules that form duplex to duplex crosslinks in DNAin Chemical Communications49.pp. 9113 Full Text UEA Repository(Article) Howell, L., Bowater, R., O'Connell, M., Reszka, A., Neidle, S., Searcey, M.(2012)Synthesis of Small Molecules Targeting Multiple DNA Structures using Click Chemistryin ChemMedChem7.pp. 792-804 Full Text UEA Repository(Article) Howell, L., Waller, Z., Bowater, R., O'Connell, M., Searcey, M.(2011)A small molecule that induces assembly of a four way DNA junction at low temperaturein Chemical Communications47.pp. 8262-8264 Full Text UEA Repository(Article) Howell, L., Gulam, R., Mueller, A., O'Connell, M., Searcey, M.(2010)Design and synthesis of threading intercalators to target DNAin Bioorganic & Medicinal Chemistry Letters1.pp. 6956-6959 Full Text UEA Repository(Article) Howell, L., Searcey, M.(2009)Targeting Higher-Order DNA: Beyond the G-Quadruplexin ChemBioChem10.pp. 2139-2143 Full Text UEA Repository(Article) Howell, L., Howman, A., O'Connell, M., Mueller, A., Searcey, M.(2009)Synthesis and evaluation of 9-aminoacridines derived from benzyne click chemistryin Bioorganic & Medicinal Chemistry Letters19.pp. 5880-5883 Full Text UEA Repository(Article)