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Research

Publications: Dr Lesley Howell

Howell LA, Beekman AM ( 2020 ) . In silico peptide-directed ligand design complements experimental peptide-directed binding for protein–protein interaction modulator discovery . RSC Chemical Biology
Moreno-Delgado D, Puigdellívol M, Moreno E, Rodríguez-Ruiz M, Botta J, Gasperini P, Chiarlone A, Howell LA et al. ( 2020 ) . Modulation of dopamine D1 receptors via histamine H3 receptors is a novel therapeutic target for Huntington's disease . eLife vol. 9 , 1 - 31 .
Botta J, Bibic L, Killoran P, McCormick PJ, Howell LA ( 2019 ) . Design and development of stapled transmembrane peptides that disrupt the activity of G-protein coupled receptor oligomers . J Biol Chem
Mills SC, HOWELL LA, Beekman A, Stokes L, Mueller A ( 2017 ) . Rac1 plays a role in CXCL12 but not CCL3-induced chemotaxis and Rac1 GEF inhibitor NSC23766 has off target effects on CXCR4 . Cellular Signalling
Beekman AM, O'Connell MA, Howell LA ( 2017 ) . Peptide‐Directed Binding for the Discovery of Modulators of α‐Helix‐Mediated Protein–Protein Interactions: Proof‐of‐Concept Studies with the Apoptosis Regulator Mcl‐1 . Angewandte Chemie vol. 129 , ( 35 ) 10582 - 10586 .
HOWELL LA, Beekman A, O'Connell MA ( 2017 ) . Peptide directed binding; a novel approach for the discovery of modulators of alpha-helix mediated protein-protein interactions demonstrated with apoptosis regulating Mcl-1 . Angewandte Chemie International Edition
HOWELL LA, Moreno E, Chiarlone A, Medrano M, Puigdellívol M, Bibic L, Resel E, Puente N et al. ( 2017 ) . Singular Location and Signaling Profile of Adenosine A2A-Cannabinoid CB1 Receptor Heteromers in the Dorsal Striatum . Neuropsychopharmacology (Nature)
Busnelli M, Kleinau G, Muttenthaler M, Stoev S, Manning M, Bibic L, Howell LA, McCormick PJ et al. ( 2016 ) . Design and Characterization of Superpotent Bivalent Ligands Targeting Oxytocin Receptor Dimers via a Channel-Like Structure . Journal of Medicinal Chemistry vol. 59 , ( 15 ) 7152 - 7166 .
Beekman AM, O'Connell MA, Howell LA ( 2016 ) . Identification of Small-Molecule Inhibitors of the Antiapoptotic Protein Myeloid Cell Leukaemia-1 (Mcl-1) . ChemMedChem vol. 11 , ( 8 ) 840 - 844 .
Beekman AM, Howell LA ( 2016 ) . Small-Molecule and Peptide Inhibitors of the Pro-Survival Protein Mcl-1 . ChemMedChem vol. 11 , ( 8 ) 802 - 813 .
Angulo J, Goffin SA, Gandhi D, Searcey M, Howell LA ( 2016 ) . Unveiling the "three-Finger Pharmacophore" Required for p53-MDM2 Inhibition by Saturation-Transfer Difference (STD) NMR Initial Growth-Rates Approach . Chemistry - A European Journal vol. 22 , ( 17 ) 5858 - 5862 .
Austin MJ, Hearnshaw SJ, Mitchenall LA, McDermott PJ, Howell LA, Maxwell A, Searcey M ( 2016 ) . A natural product inspired fragment-based approach towards the development of novel anti-bacterial agents . MedChemComm vol. 7 , ( 7 ) 1387 - 1391 .
Cominetti MMD, Goffin SA, Raffel E, Turner KD, Ramoutar JC, O'Connell MA, Howell LA, Searcey M ( 2015 ) . Identification of a new p53/MDM2 inhibitor motif inspired by studies of chlorofusin . Bioorganic and Medicinal Chemistry Letters vol. 25 , ( 21 ) 4878 - 4880 .
Viñals X, Moreno E, Lanfumey L, Cordomí A, Pastor A, De La Torre R, Gasperini P, Navarro G et al. ( 2015 ) . Cognitive impairment induced by delta9- tetrahydrocannabinol occurs through heteromers between cannabinoid CB<inf>1</inf> and serotonin 5-HT<inf>2A</inf> receptors . PLoS Biology vol. 13 , ( 7 )
Navarro G, Quiroz C, Moreno-Delgado D, Sierakowiak A, McDowell K, Moreno E, Rea W, Cai NS et al. ( 2015 ) . Orexin–corticotropin-releasing factor receptor heteromers in the ventral tegmental area as targets for cocaine . Journal of Neuroscience vol. 35 , ( 17 ) 6639 - 6653 .
Waller ZAE, Howell LA, Macdonald CJ, O'Connell MA, 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) . Biochemical and Biophysical Research Communications vol. 447 , ( 1 ) 128 - 132 .
Rackham BD, Howell LA, Round AN, Searcey M ( 2013 ) . Non-covalent duplex to duplex crosslinking of DNA in solution revealed by single molecule force spectroscopy . Organic and Biomolecular Chemistry vol. 11 , ( 48 ) 8340 - 8347 .
Marín MJ, Rackham BD, Round AN, Howell LA, Russell DA, Searcey M ( 2013 ) . A rapid screen for molecules that form duplex to duplex crosslinks in DNA . Chemical Communications vol. 49 , ( 80 ) 9113 - 9115 .
Howell LA, Bowater RA, O'Connell MA, Reszka AP, Neidle S, Searcey M ( 2012 ) . Synthesis of Small Molecules Targeting Multiple DNA Structures using Click Chemistry . ChemMedChem vol. 7 , ( 5 ) 792 - 804 .
Howell LA, Waller ZAE, Bowater R, O'Connell M, Searcey M ( 2011 ) . A small molecule that induces assembly of a four way DNA junction at low temperature . Chemical Communications vol. 47 , ( 29 ) 8262 - 8264 .
Howell LA, Gulam R, Mueller A, O'Connell MA, Searcey M ( 2010 ) . Design and synthesis of threading intercalators to target DNA . Bioorganic and Medicinal Chemistry Letters vol. 20 , ( 23 ) 6956 - 6959 .
Howell LA, Howman A, O'Connell MA, Mueller A, Searcey M ( 2010 ) . ChemInform Abstract: Synthesis and Evaluation of 9‐Aminoacridines Derived from Benzyne Click Chemistry . ChemInform vol. 41 , ( 7 )
Howell LA, Searcey M ( 2009 ) . ChemInform Abstract: Targeting Higher‐Order DNA: Beyond the G‐Quadruplex . ChemInform vol. 40 , ( 50 )
Howell LA, Howman A, O'Connell MA, Mueller A, Searcey M ( 2009 ) . Synthesis and evaluation of 9-aminoacridines derived from benzyne click chemistry . Bioorganic and Medicinal Chemistry Letters vol. 19 , ( 20 ) 5880 - 5883 .
Howell LA, Searcey M ( 2009 ) . Targeting higher-order DNA: Beyond the G-quadruplex . ChemBioChem vol. 10 , ( 13 ) 2139 - 2143 .