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.
Evidence from kinetic isotope studies for an enolate intermediate in the mechanism of type II dehydroquinases.
JM Harris, C GonzalezBello, C Kleanthous, AR Hawkins, JR Coggins, C Abell - Biochem J (1996) 319, 333
Comparison of the substrate specificity of type I and type II dehydroquinases with 5-deoxy- and 4,5-dideoxy-dehydroquinic acid
JM Harris, WJ Watkins, AR Hawkins, JR Coggins, C Abell - J CHEM SOC PERK T 1 (
1996), 2371
(DOI:
10.1039/p19960002371)
An electrochemical study to model the chorismate synthase reaction
ME Theoclitou, PJ Duggan, C Abell - BIOORG MED CHEM LETT (
1996)
6, 1285
(DOI:
10.1016/0960-894X(96)00217-X)
Approaches to antibody-catalyzed cationic cyclizations: Chemical studies of leaving groups and cyclization modes
C Lawrence, IM Bell, C Abell, FJ Leeper - ISRAEL J CHEM (1996) 36, 161
ENZYMATIC-SYNTHESIS OF (6R)-FLUOROSHIKIMIC ACID AND (6S)-FLUOROSHIKIMIC ACID
PJ DUGGAN, E PARKER, J COGGINS, C ABELL - BIOORG MED CHEM LETT (
1995)
5, 2347
(DOI:
10.1016/0960-894X(95)00405-I)
Escherichia coli chorismate synthase catalyzes the conversion of (6S)-6-fluoro-5-enolpyruvylshikimate-3-phosphate to 6-fluorochorismate. Implications for the enzyme mechanism and the antimicrobial action of (6S)-6-fluoroshikimate.
S BORNEMANN, MK RAMJEE, S BALASUBRAMANIAN, C ABELL, JR COGGINS, DJ LOWE, RNF THORNELEY - J Biol Chem (1995) 270, 22811
Escherichia coli chorismate synthase: a deuterium kinetic-isotope effect under single-turnover and steady-state conditions shows that a flavin intermediate forms before the C-(6proR)-H bond is cleaved.
S BORNEMANN, S BALASUBRAMANIAN, JR COGGINS, C ABELL, DJ LOWE, RNF THORNELEY - Biochem J (1995) 305 ( Pt 3), 707
ESCHERICHIA-COLI DIHYDRODIPICOLINATE SYNTHASE - CHARACTERIZATION OF THE IMINE INTERMEDIATE AND THE PRODUCT OF BROMOPYRUVATE TREATMENT BY ELECTROSPRAY MASS-SPECTROMETRY
EB BORTHWICK, SJ CONNELL, DW TUDOR, DJ ROBINS, A SHNEIER, C ABELL, JR COGGINS - BIOCHEMICAL JOURNAL (1995) 305, 521
Observation of a secondary tritium isotope effect in the chorismate synthase reaction.
S BALASUBRAMANIAN, JR COGGINS, C ABELL - Biochemistry (
1995)
34, 341
(DOI:
10.1021/bi00001a042)
The resolution of diterpene cyclase activities from Ricinus communis
CM SPICKETT, K PONNAMPERUMA, C ABELL - Phytochemistry (
1994)
37, 971
(DOI:
10.1016/S0031-9422(00)89511-4)