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.
Rapid screening by MALDI-TOF mass spectrometry to probe binding specificity at enzyme active sites.
ME Webb, E Stephens, AG Smith, C Abell - Chemical Communications (
2003)
9, 2416
(DOI:
10.1039/b308182f)
Enzymic synthesis of 3-[3- 13C]dehydroquinic acid.
M Frederickson, EJ Parker, JR Coggins, C Abell - Org Biomol Chem (
2003)
1, 3271
(DOI:
10.1039/b309666a)
Chiral discrimination of basic and hydrophobic molecules by chemical force spectroscopy
M Mahapatro, C Gibson, C Abell, T Rayment - Ultramicroscopy (
2003)
97, 297
(DOI:
10.1016/S0304-3991(03)00055-X)
Calibration of AFM cantilever spring constants
CT Gibson, BL Weeks, C Abell, T Rayment, S Myhra - Ultramicroscopy (
2003)
97, 113
(DOI:
10.1016/S0304-3991(03)00035-4)
Multicomponent submicron features of biomolecules created by voltage controlled deposition from a nanopipet.
A Bruckbauer, DJ Zhou, LM Ying, YE Korchev, C Abell, D Klenerman - Journal of the American Chemical Society (
2003)
125, 9834
(DOI:
10.1021/ja035755v)
Structure of E-coli ketopantoate hydroxymethyl transferase complexed with ketopantoate and Mg2+, solved by locating 160 selenomethionine sites
F von Delft, T Inoue, SA Saldanha, HH Ottenhof, F Schmitzberger, LM Birch, V Dhanaraj, M Witty, AG Smith, TL Blundell, C Abell - Structure (
2003)
11, 985
(DOI:
10.1016/S0969-2126(03)00158-8)
Comparative analysis of the Escherichia coli ketopantoate hydroxymethyltransferase crystal structure confirms that it is a member of the (betaalpha)8 phosphoenolpyruvate/pyruvate superfamily.
F Schmitzberger, AG Smith, C Abell, TL Blundell - J Bacteriol (
2003)
185, 4163
(DOI:
10.1128/JB.185.14.4163-4171.2003)
Design, synthesis and evaluation of bifunctional inhibitors of type II dehydroquinase
MD Toscano, M Frederickson, DP Evans, JR Coggins, C Abell, C Gonzalez-Bello - Org Biomol Chem (
2003)
1, 2075
(DOI:
10.1039/b301731a)
Structural insights into the evolution of the pantothenate-biosynthesis pathway.
CMC Lobley, F Schmitzberger, ML Kilkenny, H Whitney, HH Ottenhof, E Chakauya, ME Webb, LM Birch, KL Tuck, C Abell, AG Smith, TL Blundell - Biochem Soc Trans (
2003)
31, 563
(DOI:
10.1042/BST0310563)
Experiences with the Shikimate-pathway enzymes as targets for rational drug design
JR Coggins, C Abell, LB Evan, M Frederickson, DA Robinson, AW Roszak, AP Lapthorn - BIOCHEMICAL SOCIETY TRANSACTIONS (
2003)
31, 548
(DOI:
10.1042/BST0310548)