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.
Application of fragment growing and fragment linking to the discovery of inhibitors of Mycobacterium tuberculosis pantothenate synthetase.
AW Hung, HL Silvestre, SJ Wen, A Ciulli, TL Blundell, C Abell - Angew Chem Int Ed Engl (
2009)
48, 8452
(DOI:
10.1002/anie.200903821)
Inhibition of Mycobacterium tuberculosis Pantothenate Synthetase by Analogues of the Reaction Intermediate
A Ciulli, DE Scott, M Ando, F Reyes, SA Saldanha, KL Tuck, DY Chirgadze, TL Blundell, C Abell - Chembiochem (
2008)
9, 2606
(DOI:
10.1002/cbic.200800437)
Towards engineering increased pantothenate (vitamin B5) levels in plants
E Chakauya, KM Coxon, M Wei, MV MacDonald, T Barsby, C Abell, AG Smith - Plant Mol Biol (
2008)
68, 493
(DOI:
10.1007/s11103-008-9386-5)
Nanomechanical detection of antibiotic mucopeptide binding in a model for superbug drug resistance
JW Ndieyira, M Watari, AD Barrera, D Zhou, M Vogtli, M Batchelor, MA Cooper, T Strunz, MA Horton, C Abell, T Rayment, G Aeppli, RA Mckendry - Nature Nanotechnology (
2008)
3, 691
(DOI:
10.1038/nnano.2008.275)
Development of quantitative cell-based enzyme assays in microdroplets.
A Huebner, LF Olguin, D Bratton, G Whyte, WTS Huck, AJ de Mello, JB Edel, C Abell, F Hollfelder - Analytical Chemistry (
2008)
80, 3890
(DOI:
10.1021/ac800338z)
A compact functional quantum dot-DNA conjugate: Preparation, hybridization, and specific label-free DNA detection
DJ Zhou, LM Ying, X Hong, EA Hall, C Abell, D Klenerman - Langmuir (
2008)
24, 1659
(DOI:
10.1021/la703583u)
Single-step biocompatible coating for sulfhydryl coupling of receptors using 2-(pyridinyldithio)ethylcarbamoyl dextran.
X Li, C Abell, MA Cooper - Colloids and Surfaces B: Biointerfaces (
2008)
61, 113
(DOI:
10.1016/j.colsurfb.2007.06.026)
An integrated device for monitoring time-dependent in vitro expression from single genes in picolitre droplets
F Courtois, LF Olguin, G Whyte, D Bratton, WTS Huck, C Abell, F Hollfelder - Chembiochem (
2008)
9, 439
(DOI:
10.1002/cbic.200700536)
From microdroplets to microfluidics: Selective emulsion separation in microfluidic devices
LM Fidalgo, G Whyte, D Bratton, CF Kaminski, C Abell, WTS Huck - Angew Chem Int Ed Engl (
2008)
47, 2042
(DOI:
10.1002/anie.200704903)
Discovery and Extrapolation of Fragment Structures towards Drug Design
A Ciulli, TL Blundell, C Abell - (2008), 16
