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.
Using a Fragment-Based Approach To Target Protein-Protein Interactions
DE Scott, MT Ehebauer, T Pukala, M Marsh, TL Blundell, AR Venkitaraman, C Abell, M Hyvönen - Chembiochem (
2013)
14, 332
(DOI:
10.1002/cbic.201200521)
Discovery of Schaeffer's Acid Analogues as Lead Structures of Mycobacterium tuberculosis TypeII Dehydroquinase Using a Rational Drug Design Approach
MF Schmidt, O Korb, NI Howard, MVB Dias, TL Blundell, C Abell - ChemMedChem (
2013)
8, 54
(DOI:
10.1002/cmdc.201200508)
Hierarchical virtual screening for the discovery of new molecular scaffolds in antibacterial hit identification.
PJ Ballester, M Mangold, NI Howard, RL Marchese Robinson, C Abell, J Blumberger, OBO Mitchell - J R Soc Interface (
2012)
9, 3196
(DOI:
10.1098/rsif.2012.0569)
Using ligand-mapping simulations to design a ligand selectively targeting a cryptic surface pocket of polo-like kinase 1
YS Tan, P Śledź, S Lang, CJ Stubbs, DR Spring, C Abell, RB Best - Angew Chem Int Ed Engl (
2012)
51, 10078
(DOI:
10.1002/anie.201205676)
Application of Fragment Screening and Merging to the Discovery of Inhibitors of the Mycobacterium tuberculosis Cytochrome P450 CYP121
SA Hudson, KJ McLean, S Surade, Y-Q Yang, D Leys, A Ciulli, AW Munro, C Abell - Angew Chem Int Ed Engl (
2012)
51, 9311
(DOI:
10.1002/anie.201202544)
Probing riboswitch-ligand interactions using thiamine pyrophosphate analogues
L Chen, E Cressina, N Dixon, K Erixon, K Agyei-Owusu, J Micklefield, AG Smith, C Abell, FJ Leeper - Organic and Biomolecular Chemistry (
2012)
10, 5924
(DOI:
10.1039/c2ob07116a)
Fabrication of Microgel Particles with Complex Shape via Selective Polymerization of Aqueous Two-Phase Systems
S Ma, J Thiele, X Liu, Y Bai, C Abell, WTS Huck - Small (
2012)
8, 2356
(DOI:
10.1002/smll.201102715)
Pathway-selective sensitization of mycobacterium tuberculosis for target-based whole-cell screening
GL Abrahams, A Kumar, S Savvi, AW Hung, S Wen, C Abell, CE Barry III, DR Sherman, HIM Boshoff, V Mizrahi - Chemistry and Biology (
2012)
19, 844
(DOI:
10.1016/j.chembiol.2012.05.020)
High-Throughput Interrogation of Ligand Binding Mode Using a Fluorescence-Based Assay
P Śledź, S Lang, CJ Stubbs, C Abell - Angew Chem Int Ed Engl (
2012)
51, 7680
(DOI:
10.1002/anie.201202660)
Fragment-Based Approaches in Drug Discovery and Chemical Biology
DE Scott, AG Coyne, SA Hudson, C Abell - Biochemistry (
2012)
51, 4990
(DOI:
10.1021/bi3005126)
