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Volume 11
Journal of Proteomics & Bioinformatics
ISSN: 0974-276X
Structural Biology 2018
September 24-26, 2018
September 24-26, 2018 | Berlin, Germany
14
th
International Conference on
Structural Biology
Fragment based drug discovery at Astex
Judith Reeks
Astex Pharmaceuticals, UK
F
ragment-based drug discovery at Astex uses X-ray crystallography and orthogonal biophysical techniques (including NMR,
SPR, ITC and thermal shift) to detect the binding of low molecular weight fragments (<300 Da) to proteins. Although the
detected fragment ‘hits’ bind weakly (mM), their small size permits the formation of optimal interactions with the target
protein and the fragments serve as valuable starting points for rational drug design. Hits with good growth vectors can be
chemically elaborated into potent ligands through fast, iterative rounds of structure-based design. This approach allows for
the control, and optimisation, of ligand potency, selectivity, and physicochemical properties. This poster will describe the key
aspects of fragment-based drug discovery at Astex, illustrated by the fragment screening that led to potent, selective inhibitors
of ERK1/2.
Recent Publications:
1. Tan Y S, Reeks J et al. (2016) Benzene probes in molecular dynamics simulations reveal novel binding sites for ligand
design. Journal of Physical Chemistry Letters 7:3452-7.
2. Reeks J et al. (2013) Structure of the archaeal Cascade subunit Csa5: relating the small subunits of CRISPR effector
complexes. RNA Biology 10:762-9.
3. Reeks J et al. (2013) CRISPR interference: a structural perspective. Biochemical Journal 453:155-166.
4. Reeks J et al. (2013) Structure of a dimeric crenarchaeal Cas6 enzyme with an atypical active site for CRISPR RNA
processing. Biochemical Journal 452:223-230.
5. Zhang et al. (2012) Structure and mechanism of the CMR complex for CRISPR-mediated antiviral immunity.
Molecular Cell 45:303-313.
Biography
Judith Reeks is a Research Associate in the Molecular Sciences Department of Astex Pharmaceuticals. Her main focus is using x-ray crystallography for drug
discovery. She gained a PhD from the University of St Andrews for the study of Structural Biology of CRISPR-associated proteins and then moved to the Northern
Institute for Cancer Research as a Post-doctoral research associate working on drug discovery projects.
Judith Reeks, J Proteomics Bioinform 2018, Volume 11
DOI: 10.4172/0974-276X-C2-116