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.
Probing hot spots at protein-ligand binding sites: a fragment-based approach using biophysical methods.
A Ciulli, G Williams, AG Smith, TL Blundell, C Abell - J Med Chem (
2006)
49, 4992
(DOI:
10.1021/jm060490r)
Building three-dimensional nanostructures with active enzymes by surface templated layer-by-layer assembly.
S Rauf, DJ Zhou, C Abell, D Klenerman, DJ Kang - Chemical Communications (
2006), 1721
(DOI:
10.1039/b517557g)
Crystal structures of Yersinia enterocolitica salicylate synthase and its complex with the reaction products salicylate and pyruvate
O Kerbarh, DY Chirgadze, TL Blundell, C Abell - Journal of Molecular Biology (
2006)
357, 524
(DOI:
10.1016/j.jmb.2005.12.078)
Pantothenate biosynthesis in higher plants: Advances and challenges
E Chakauya, KM Coxon, HM Whitney, JL Ashurst, C Abell, AG Smith - Physiologia Plantarum (
2006)
126, 319
(DOI:
10.1111/j.1399-3054.2006.00683.x)
Macroscopic 2D networks self-assembled from nanometer-sized protein/DNA complexes
M Manzanera, DJ Frankel, HT Li, DJ Zhou, A Bruckbauer, P Kreutzmann, JM Blackburn, C Abell, T Rayment, D Klenerman, PD Barker - Nano Lett (
2006)
6, 365
(DOI:
10.1021/nl051599+)
Application of fragment screening and fragment linking to the discovery of novel thrombin inhibitors.
N Howard, C Abell, W Blakemore, G Chessari, M Congreve, S Howard, H Jhoti, CW Murray, LCA Seavers, RLM van Montfort - J Med Chem (
2006)
49, 1346
(DOI:
10.1021/jm050850v)
A reversible pH-driven DNA nanoswitch array
DS Liu, A Bruckbauer, C Abell, S Balasubramanian, DJ Kang, D Klenerman, DJ Zhou - Journal of the American Chemical Society (
2006)
128, 2067
(DOI:
10.1021/ja0568300)
Electrostatic orientation of enzymes on surfaces for ligand screening probed by force spectroscopy
XZ Wang, DJ Zhou, K Sinniah, C Clarke, L Birch, HT Li, T Rayment, C Abell - Langmuir (
2006)
22, 887
(DOI:
10.1021/la0525731)
Design and synthesis of aromatic inhibitors of anthranilate synthase.
RJ Payne, EMM Bulloch, AD Abell, C Abell - Organic and Biomolecular Chemistry (
2005)
3, 3629
(DOI:
10.1039/b510633h)
Fluorescence resonance energy transfer between a quantum dot donor and a dye acceptor attached to DNA
DJ Zhou, JD Piper, C Abell, D Klenerman, DJ Kang, LM Ying - Chemical Communications (
2005), 4807
(DOI:
10.1039/b508911e)
