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.
Crystal Structure of Escherichia coli Enterobactin-specific Isochorismate Synthase (EntC) Bound to its Reaction Product Isochorismate: Implications for the Enzyme Mechanism and Differential Activity of Chorismate-utilizing Enzymes
S Sridharan, N Howard, O Kerbarh, M Blaszczyk, C Abell, TL Blundell - Journal of Molecular Biology (
2010)
397, 290
(DOI:
10.1016/j.jmb.2010.01.019)
Vancomycin dimer formation between analogues of bacterial peptidoglycan surfaces probed by force spectroscopy
M Batchelor, DJ Zhou, MA Cooper, C Abell, T Rayment - Organic and Biomolecular Chemistry (
2010)
8, 1142
(DOI:
10.1039/b919347b)
Synthesis of novel fluorous surfactants for microdroplet stabilisation in fluorous oil streams
DJ Holt, RJ Payne, C Abell - Journal of Fluorine Chemistry (
2010)
131, 398
(DOI:
10.1016/j.jfluchem.2009.12.010)
Tri-partite complex for axonal transport drug delivery achieves pharmacological effect
AG Filler, GT Whiteside, M Bacon, M Frederickson, FA Howe, MD Rabinowitz, AJ Sokoloff, TW Deacon, C Abell, R Munglani, JR Griffiths, BA Bell, AML Lever - BMC Neuroscience (
2010)
11, 8
(DOI:
10.1186/1471-2202-11-8)
A fragment-based approach to probing adenosine recognition sites by using dynamic combinatorial chemistry.
DE Scott, GJ Dawes, M Ando, C Abell, A Ciulli - Chembiochem (
2009)
10, 2772
(DOI:
10.1002/cbic.200900537)
Simultaneous Determination of Gene Expression and Enzymatic Activity in Individual Bacterial Cells in Microdroplet Compartments
JU Shim, LF Olguin, G Whyte, D Scott, A Babtie, C Abell, WTS Huck, F Hollfelder - Journal of the American Chemical Society (
2009)
131, 15251
(DOI:
10.1021/ja904823z)
Biofunctionalized protein resistant oligo(ethylene glycol)-derived polymer brushes as selective immobilization and sensing platforms.
J Trmcic-Cvitas, E Hasan, M Ramstedt, X Li, MA Cooper, C Abell, WTS Huck, JE Gautrot - Biomacromolecules (
2009)
10, 2885
(DOI:
10.1021/bm900706r)
Simultaneous measurement of reactions in microdroplets filled by concentration gradients
N Damean, LF Olguin, F Hollfelder, C Abell, WTS Huck - Lab on a Chip (
2009)
9, 1707
(DOI:
10.1039/b821021g)
Synthesis and evaluation of 2,5-dihydrochorismate analogues as inhibitors of the chorismate-utilising enzymes.
RJ Payne, EMM Bulloch, MM Toscano, MA Jones, O Kerbarh, C Abell - Organic and Biomolecular Chemistry (
2009)
7, 2421
(DOI:
10.1039/b901694e)
An integrated cell culture lab on a chip: modular microdevices for cultivation of mammalian cells and delivery into microfluidic microdroplets
H Hufnagel, A Huebner, C Gulch, K Guse, C Abell, F Hollfelder - Lab on a Chip (
2009)
9, 1576
(DOI:
10.1039/b821695a)
