The University of York consists of a number of large Departments with a total of over 16,000 students. The FragNet consortium is centred around the York Structural Biology Laboratory – a large grouping of over 70 scientists with a long tradition of research excellence in the methods of protein structure analysis and exploitation. YSBL is at the interface between the Chemistry and Biology Departments and the York-based ESRs and the interns will be assigned to supervisors from these Departments.
The University of York is situated 250 km north of London near to the spectacular scenery of the Yorkshire Dales and the North York Moors. York is a city with over 2000 years of history. It was a major strategic centre for the Romans (AD100-400), a vibrant trading centre for the Vikings (AD700-1000) and during the Middle Ages (AD1200-1500) became a major centre for commerce and the church. This history is reflected in the many ancient buildings and the city walls. Today, York has a population of around 150,000 with major employment in tourism and science (the University and various government agencies).
Website: University of York
Staff involved in this project:
Prof. Peter O’Brien joined the University of York in 1996 and was promoted to Professor in 2007. He is the recipient of the RSC Organic Stereochemistry Prize (2013 – for development and applications of the (+)-sparteine surrogate), a GlaxoWellcome Award (2000) and the RSC Meldola Medal (1999). He has published 125 papers and has a h-index of 32. In research since 2010, the O’Brien group have reported the first high yielding asymmetric lithiation-trapping of N-Boc piperidine, synthetic reactions showing that (+)-sparteine surrogate complexed to i-PrLi or s-BuLi in THF whereas (–)-sparteine did not (with Hilmersson), synthesis of 3-D lead-like scaffolds using N-Boc α-lithiation (with Hubbard) and the preparation of enantiomerically pure Grignard reagents. Recently, O’Brien has pioneered the use of in situ React IR spectroscopy to monitor the lithation of N-Boc heterocycles, work carried out via collaborations with Merck (USA), AstraZeneca and Lilly including the first example of real-time monitoring of N-Boc rotamer interconversion using in situ React IR (with Coldham). Currently, the group has two research themes: (i) discovery of new asymmetric α-lithiation methodology and application in medicinal chemistry; (ii) design, synthesis and evaluation of 3-D fragments for the systematic exploration of 3-D pharmaceutical space – a project supported by a pharmaceutical consortium (Astex, AstraZeneca, Lilly, Pfizer and Vernalis).
Prof. Rod Hubbard has been at the University of York for over 35 years. During the 1980s, his main research interests were the development of molecular graphics and modelling methods, leading to the programs HYDRA and QUANTA which were used worldwide. Some of this work was while on sabbatical in Harvard where he worked with Martin Karplus, including some of the first use of computational methods to exploit fragments that can bind to protein active sites. During the 1990s, he helped to build and develop the York Structural Biology Laboratory as a major centre for protein structure analysis. This included many productive collaborations with pharmaceutical and biotechnology companies such as Novo Nordisk, GSK, Celltech, Chiroscience, Pfizer, KaroBio and Peptide Therapeutics) working on therapeutically important proteins. This led to interests in exploring protein-ligand interactions and how to use protein structure for drug discovery. He took the opportunity in 2001 to spend some time at the company RiboTargets (now Vernalis) to establish structure and fragment based methods in a real drug discovery environment. He has continued to split his time between York and Vernalis. His personal research in York is on development and use of discovery methods for chemical biology and the three main research areas reflect the ESR projects available: (1) discovery of activators of industrial enzymes, (2) design and application of novel 3D fragments, (3) probing the bacterial replisome for druggable sites.