研究领域

Biological

One of the biggest challenges in biological chemistry is the design of small molecules that interact selectively with macromolecules. We are pioneering the development of the use of fragments to address this challenge. This approach involves close synergistic interaction between synthetic organic chemistry, biophysics and structural biology. We are using fragment-based methods to identify inhibitors of enzymes from Mycobacterium tuberculosis, and to develop small molecules that modulate protein-protein interactions. We are also keen to explore new applications for fragments e.g. to identify molecules that modulate the activity of riboswitches, and to assign function to orphan proteins. Our second major area of research is to develop the use of microdroplets in microfluidics as a novel experimental platform for biological chemistry. This research is highly interdisciplinary and involves biological chemistry, microfluidics, nanofabrication, laser spectroscopy and mass spectrometry. We are particularly interested in looking at cells in droplets, e.g. bacteria to study quorum sensing, algae for bio-fuel development.

近期论文

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Design and structural analysis of aromatic inhibitors of Type II dehydroquinase from mycobacterium tuberculosis. N I Howard, M V Dias, F Peyrot, L Chen, M F Schmidt, T L Blundell, C Abell. ChemMedChem, 2015, 10 (1), 116-133. 10.1002/cmdc.201402298 Interfacial assembly of dendritic microcapsules with host-guest chemistry. Y Zheng, Z Yu, R M Parker, Y Wu, C Abell, O A Scherman Ncomms, 2014, 55, 5772. 10.1038/ncomms6772 Small-molecule inhibitors that target protein-protein interactions in the RAD51 family of recombinases. D E Scott, A G Coyne, A G Venkitaramen, T L Blundell, C Abell, M Hyvönen. ChemMedChem, 2014, 10 (1), 116-133. 10.1002/cmdc.201402428. Epub ahead of print Binding hotspots of BAZ2B bromodomain: Histone interaction revealed by solution NMR driven docking F M Ferguson, D M Dias, J P Rodrigues, H Wienk, H Boelens, A M Bonvin, C Abell, A Ciulli. Biochemistry,2014, 53 (42), 6706-6716. 10.1021/bi500909d Evolution of enzyme catalysts caged in biomimetic gel-shell beads. M Fischlechner, Y Schaerli, M F Mohamed, S Patil, C Abell, F Hollfelder. Nat Chem, 2014, 6 (9), 791-796. 10.1038/nchem.1996 Regioselective conversion of arenes to N-aryl-1.2.3-triazoles using C-H borylation. R Srinivasen, A G Coyne, C Abell. Chem Eur J, 2014, 20, 11680-11684. 10.1002/chem.201403021 Pantothenic acid biosynthesis in the parasite Toxoplasma gondii: a target for chemotherapy. S N Mageed, F Cunningham, A W Hung, H L Silvestre, S Wen, T L Blundell, C Abell, G A McConkey. C., 2014, 02640-14. 10.1128/AAC.02640-14 The use of chlorobenzene as a probe molecule in molecular dynamics simulations. Y S Tan, D R Spring, C Abell, C Verma. J. Chem. Inf. Model., 2014. 10.1021/ci500215x Supramolecular colloidosomes: fabrication, characterisation and triggered release of cargo. G Stephenson, R M Parker, Y Lan, Z Yu, O A Scherman, C Abell. Chem Commun., 2014, 50, 7048-7051. 10.1039/C4CC01479K Validating fragment-based drug discovery for biological RNAs: lead fragments bind and remodel the TPP riboswitch specifically. K D Warner, P Homan, K M Weeks, A G Smith, C Abell, A R Ferré -D'Amaré. Chem Biol., 2014, 21, 591-595. 10.1016/j.chembiol.2014.03.007 Threonine 57 is required for the post-translational activation of Escherichia coli aspartate α-decarboxylase. M E Webb, B A Yorke, T Kershaw, S Lovelock, C M Lobley, M L Kilkenny, A G Smith, T L Blundell, A R Pearson, C Abell. Acta Cryst., 2014, D70, 1166-1172. 10.1107/S1399004713034275 Surface-stress sensors for rapid and ultrasensitive detection of active free drugs in human serum. J W Ndieyira, N Kappeler, S Logan, M A Cooper, C Abell, R A McKendry, G Aeppli. Nat Nanotechnol, 2014, 9, 225-232. 10.1038/nnano.2014.33 Biofragments: an approach towards predicting protein function using biologically related fragments and its application to mycobacterium tuberculosis CYP126. S A Hudson, E H Mashalidis, A Bender, K J McLean, A W Munro, C Abell. ChemBioChem, 2014, 5, 549-555. 10.1002/cbic.201300697 Real time dual-channel multiplex SERS ultradetection. S Abalde-Cela, C Abell, R A Alvarez-Puebla, L M Liz-Marzán. J. Phys. Chem. Lett., 2014, 5, 73-79. 10.1021/jz402419k Targeting a c-MYC G-quadruplex DNA with a fragment library. H R Nasiri, N M Bell, K I McLuckie, J Husby, C Abell, S Neidle, S Balasubramanian. Chem Commun, 2014, 50, 1704-1707. 10.1039/C3CC48390H Targeting low-druggability bromodomains: fragment based screening and inhibitor design against the BAZ2B bromodomain. F M Ferguson, O Fedorov, A Chaikuad, M Philpott, J R Muniz, I Felletar, F von Delft, T Heighton, S Knapp, C Abell, A Ciulli. J Med Chem, 2013, 56, 10183-10187. DOI: 10.1021/jm401582c A three-stage biophysical screening cascade for fragment-based drug discovery. E H Mashalidis, P Śledź, S Lang, C Abell. Nature Protocols, 2013, 8, 2309-2324. DOI: 10.1038/nprot.2013.130 MicroRNA-Specific Argonaute 2 Protein Inhibitors. M F Schmidt, O Korb, C Abell. ACS Chem Biol, 2013, 8, 2122-2126. DOI: 10.1021/cb400246k Ultrarapid generation of femtoliter microfluidic droplets for single-molecule-counting immunoassays. J U Shim, R T Ranasinghe, C A Smith, S M Ibrahim, F Hollfelder, W T Huck, D Klenerman, C Abell. ACS Nano, 2013, 7, 5955-5964. DOI: 10.1021/nn401661d Integrated biophysical approach to fragment screening and validation for fragment-based lead discovery. H L Silvestre, T L Blundell, C Abell, A Ciulli. Proc. Natl. Acad. Sci. U.S.A, 2013, 110, 12984-9. DOI: 10.1073/pnas.1304045110 Overcoming the limitations of fragment merging: rescuing a strained merged fragment series targeting Mycobacterium tuberculosis CYP121. S A Hudson, S Surade, A G Coyne, K J McLean, D Leys, A W Munro, C Abell. ChemMedChem, 2013, 8, 1451-1456. DOI: 10.1002/cmdc.201300219