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.
MicroRNA-Specific Argonaute 2 Protein Inhibitors.
MF Schmidt, O Korb, C Abell - ACS Chem Biol (
2013), 130731134658005
(DOI:
10.1021/cb400246k)
Integrated biophysical approach to fragment screening and validation for fragment-based lead discovery
HL Silvestre, TL Blundell, C Abell, A Ciulli - Proceedings of the National Academy of Sciences of the United States of America (
2013)
110, 12984
(DOI:
10.1073/pnas.1304045110)
Overcoming the Limitations of Fragment Merging: Rescuing a Strained Merged Fragment Series Targeting Mycobacterium tuberculosis CYP121
SA Hudson, S Surade, AG Coyne, KJ Mclean, D Leys, AW Munro, C Abell - ChemMedChem (
2013)
8, n/a
(DOI:
10.1002/cmdc.201300219)
Nanoelectrospray Ionization Mass Spectrometric Study of Mycobacterium tuberculosis CYP121-Ligand Interactions
KM Duffell, SA Hudson, KJ McLean, AW Munro, C Abell, D Matak-Vinković - Analytical Chemistry (
2013)
85, 5707
(DOI:
10.1021/ac400236z)
Ultrarapid generation of femtoliter microfluidic droplets for single-molecule-counting immunoassays
J-U Shim, RT Ranasinghe, CA Smith, SM Ibrahim, F Hollfelder, WTS Huck, D Klenerman, C Abell - ACS Nano (
2013)
7, 5955
(DOI:
10.1021/nn401661d)
Intra-species bacterial quorum sensing studied at single cell level in a double droplet trapping system
Y Bai, SN Patil, SD Bowden, S Poulter, J Pan, GPC Salmond, M Welch, WTS Huck, C Abell - International Journal of Molecular Sciences (
2013)
14, 10570
(DOI:
10.3390/ijms140510570)
Sensitive, High Throughput Detection of Proteins in Individual, Surfactant-Stabilized Picoliter Droplets Using Nanoelectrospray Ionization Mass Spectrometry
CA Smith, X Li, TH Mize, TD Sharpe, EI Graziani, C Abell, WTS Huck - Analytical Chemistry (
2013)
85, 3812
(DOI:
10.1021/ac400453t)
Using a Fragment-Based Approach To Target Protein-Protein Interactions
DE Scott, MT Ehebauer, T Pukala, M Marsh, TL Blundell, AR Venkitaraman, C Abell, M Hyvönen - Chembiochem (
2013)
14, 332
(DOI:
10.1002/cbic.201200521)
Discovery of Schaeffer's Acid Analogues as Lead Structures of Mycobacterium tuberculosis TypeII Dehydroquinase Using a Rational Drug Design Approach
MF Schmidt, O Korb, NI Howard, MVB Dias, TL Blundell, C Abell - ChemMedChem (
2013)
8, 54
(DOI:
10.1002/cmdc.201200508)
Hierarchical virtual screening for the discovery of new molecular scaffolds in antibacterial hit identification.
PJ Ballester, M Mangold, NI Howard, RL Marchese Robinson, C Abell, J Blumberger, OBO Mitchell - J R Soc Interface (
2012)
9, 3196
(DOI:
10.1098/rsif.2012.0569)
