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.
Surface-induced droplet fusion in microfluidic devices
LM Fidalgo, C Abell, WTS Huck - Lab on a Chip (
2007)
7, 984
(DOI:
10.1039/b708091c)
Rational design, synthesis, and evaluation of nanomolar type II dehydroquinase inhibitors
RJ Payne, F Peyrot, O Kerbarh, AD Abell, C Abell - ChemMedChem (
2007)
2, 1015
(DOI:
10.1002/cmdc.200700032)
Fragment-based approaches to inhibitor discovery: targeting cofactor-binding sites and protein-protein interactions
A Ciulli, TL Blundell, C Abell - DRUG FUTURE (2007) 32, 13
Design, synthesis, and structural studies on potent biaryl inhibitors of type II dehydroquinases
RJ Payne, A Riboldi-Tunnicliffe, O Kerbarh, AD Abell, AJ Lapthorn, C Abell - ChemMedChem (
2007)
2, 1010
(DOI:
10.1002/cmdc.200700062)
Nucleophile selectivity of chorismate-utilizing enzymes
O Kerbarh, A Ciulli, DY Chirgadze, TL Blundell, C Abell - Chembiochem (
2007)
8, 622
(DOI:
10.1002/cbic.200700019)
Quantitative detection of protein expression in single cells using droplet microfluidics
A Huebner, M Srisa-Art, D Holt, C Abell, F Hollfelder, AJ Demello, JB Edel - Chemical Communications (
2007), 1218
(DOI:
10.1039/b618570c)
pH-tuneable binding of 2'-phospho-ADP-ribose to ketopantoate reductase: a structural and calorimetric study.
A Ciulli, CMC Lobley, KL Tuck, AG Smith, TL Blundell, C Abell - Acta Crystallographica Section D Biological Crystallography (
2007)
63, 171
(DOI:
10.1107/S0907444906044465)
Crystal Structure of Escherichia coli Ketopantoate Reductase in a Ternary Complex with NADP+ and Pantoate Bound: SUBSTRATE RECOGNITION, CONFORMATIONAL CHANGE, AND COOPERATIVITY
A Ciulli, DY Chirgadze, AG Smith, TL Blundell, C Abell - J Biol Chem (
2007)
282, 8487
(DOI:
10.1074/jbc.M611171200)
Nanomolar inhibition of type II dehydroquinase based on the enolate reaction mechanism
MD Toscano, RJ Payne, A Chiba, O Kerbarh, C Abell - ChemMedChem (
2007)
2, 101
(DOI:
10.1002/cmdc.200600194)
The design and synthesis of inhibitors of pantothenate synthetase
KL Tuck, SA Saldanha, LM Birch, AG Smith, C Abell - Org Biomol Chem (
2006)
4, 3598
(DOI:
10.1039/b609482a)