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.
Targeting a c-MYC G-quadruplex DNA with a fragment library
HR Nasiri, NM Bell, KI McLuckie, J Husby, C Abell, S Neidle, S Balasubramanian – Chemical communications (Cambridge, England) (2014
Real time dual-channel multiplex SERS ultradetection
S Abalde-Cela, C Abell, RA Alvarez-Puebla, LM Liz-Marzán – Journal of Physical Chemistry Letters (2014
Targeting low-druggability bromodomains: Fragment based screening and inhibitor design against the BAZ2B bromodomain
FM Ferguson, O Fedorov, A Chaikuad, M Philpott, JR Muniz, I Felletar, F von Delft, T Heightman, S Knapp, C Abell, A Ciulli – J Med Chem (2013
A three-stage biophysical screening cascade for fragment-based drug discovery.
EH Mashalidis, P Śledź, S Lang, C Abell – Nature protocols (2013
MicroRNA-specific argonaute 2 protein inhibitors.
MF Schmidt, O Korb, C Abell – ACS Chem Biol (2013
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
Ultrarapid generation of femtoliter microfluidic droplets for single-molecule-counting immunoassays.
JU Shim, RT Ranasinghe, CA Smith, SM Ibrahim, F Hollfelder, WT Huck, D Klenerman, C Abell – ACS Nano (2013
Nanoelectrospray Ionization Mass Spectrometric Study of Mycobacterium tuberculosis CYP121-Ligand Interactions
KM Duffell, SA Hudson, KJ McLean, AW Munro, C Abell, D Matak-Vinković – Anal Chem (2013
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, GP Salmond, M Welch, WT Huck, C Abell – International journal of molecular sciences (2013
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, WT Huck – Anal Chem (2013