interview of Jean Boutin

We have been using synchrotron radiation for about 5 years. We contract companies who specialise in macromolecular crystallography to solve, on our behalf, through X-ray diffraction experiments, the 3D structures of target protein complexes /potential active principles that we supply them with. This is normal procedure in the development of new active principles that form part of new drugs. Until now the synchrotrons that we have used have usually been situated abroad.

In the area of medicinal chemistry we are always looking for the maximum information on the nature of interactions between the candidate molecule and its target. Structural data obtained from X-ray diffraction experiments are of course vital and help to guide the chemists who create these molecules, in almost a “visual” way. The enhanced performance of the beamlines requested will further improve the information provided by the 3D images by improving their resolution- the aim being to increase the power level and perhaps the selectivity of these medical candidates.
Research is also conceivable and expected both upstream and downstream in the process of obtaining new molecules, notably to characterise the crystalline forms of pure products in powder form, thanks to techniques such as SAXS. In addition, during our first exchanges, we have been able to see the potential of the different beamlines, which are not limited to X-rays: experiments using other wavelength ranges could complete studies undertaken using more traditional methods.

Our wish would be to design a joint project around a target protein which is difficult to study, for example, due to the molecule existing in several configurations or whose mechanisms of regulation are particularly complex. This project would go beyond the 3D structure of the protein. In particular, we are considering studies on living cells, for example confocal imaging of fluorescent chromophores, which certainly represents an appropriate tool for the sort of research we carry out.

In fact, the limiting factor at the moment is that we are finding it difficult to define precisely how to optimize the use of studies on the synchrotron in the context of our research. By improving our understanding of potential photon/matter interactions, we will be able to acquire the tools and adapt them to our experimental procedures. To achieve this, information on the contribution of each available technique, with data in a language adapted to the user, is a great plus.

Apart from the advantage of having a synchrotron in the proximity of our research centres, we are convinced about the wide range of techniques available and the capacity of the machine. Now it just remains to balance these against the questions that we are asking, as well as those we have not yet asked!