‘‘Synchrotron radiation is intense, polychromatic and finely collimated’’

Could you please describe the uses of different light beams in the pharma/ biotech industry?

Santosh Panjikar

Synchrotron radiation (SR) is intense, polychromatic and finely collimated. The radiation has a continuous spectrum over a broad range of frequencies – typically extending from microwave frequencies to the X-ray band. The unique properties of SR allow probing matter of widely differing nature and at very dissimilar levels of magnitude, from macroscopic assemblies to atomic structure. Pharmaceutical and biotech companies use synchrotron techniques to help develop new products at all stages of research, from drug design and formulation to pre-clinical phases. Molecular structural characterisation using X-rays forms a major proportion of the research done by pharma/biotech industry at synchrotrons, with applications ranging from macromolecular crystallography, through small molecule crystallography to high resolution powder diffraction. Macromolecular crystallography is used to study complex macromolecules and their binding to ligands with potential inhibitor effects. This is one of the most important steps in the rational drug design process.

How will you describe the benefits of using light beams over the traditional methods used for the drug discovery/ research and development?

In order to identify new lead compounds in the traditional way of drug discovery, large chemical libraries are experimentally screened against a biological target. Rational, structure-based drug design is proven to be more efficient than the traditional way of drug discovery since it aims to understand the molecular basis of a disease and utilises the knowledge of the three-dimensional crystal structure of the biological target in the process. State-of-the-art structure-based drug design methods include virtual screening and de novo drug design. These serve as an efficient, alternative approach to experimentally screening of chemical libraries against a biological target.

In order to determine crystal structure, high intense and collimated X-ray beam is required. X-rays produced by a synchrotron are 103 to 104 times brighter than the X-rays from a conventional X-ray source. Macromolecular crystallography is the gold standard technique for determining crystal structure of drug candidates but unfortunately, not all samples co-operate during crystallisation and some crystals that are too small to be studied using conventional X-ray sources. In addition, with samples that do diffract well, the benefits of the synchrotron are significantly higher resolution and very fast data collection. Because of the higher intensity of the X-rays generated, smaller crystals can be used for 3D structure determination, with samples of a few cubic microns routinely measured using the powerful and fully automated protein crystallography beamlines.

Major applications of such beams would be in the fields such as molecular and nano medicines. In India these fields are relatively in the nascent stage. So, how do you find the scope for your business in this market?

Although application of synchrotron technology for the molecule medicine field in nascent stage, however, awareness in India is increasing. On the other hand, Indian generic companies will need to compete with the multinationals by focusing on drug development and produce their own-patented products. It is realised that intellectual property issues can only be addressed by careful screening of drugs for the absence of forms patented by other companies. Already some of the major companies in India are addressing these by using Synchrotron technology. It is likely that the demand of its use will be increasing.

Do you have any tie ups with Indian universities/scientists/ scientific organisations for the research purposes?

Currently, we have collaboration with a scientist from the chemistry department of Indian Institute of Technology, Mumbai for scientific research in the area of bioremediation particularly proteins from the catabolic pathway from P. putida. Recently, Australia-Indian Council has approved limited funding for a few Indian scientists from a couple of institutions for access of beamtime at the macromolecular crystallography beamlines of Australian Synchrotron.

Have you ever organised workshops for Indian pharma/ biotech professionals/ scientist to make them understand the importance of the use of light beams in their research works?

So far we have not got an opportunity to organise any workshops for Indian professionals from industry or academics and to provide insight in the importance of the use of SR in their research works except my limited number of talks this year I have hold in a few academic institutions where macromolecular crystallography method used for their research. If there is sufficient interest in Indian pharma/ biotech and if funding becomes available such workshops can be organised.

Who are your clients in the Indian pharma/biotech industry?

We do not discuss the details of our commercial clients due to confidentiality agreement, but as India is the fastest growing market for the development of generic drugs, we have been working with some of the major companies who send their samples to us and we provide a data collection service to them.

Considering the size of the Indian pharma industry, will there be any plans of setting up your facility in India as well?

India lacks a new-generation synchrotron research facility equipped with a tunable X-ray diffraction beamline, which is necessary for the elucidation of novel macromolecular crystal structures of vital importance in biology and medicine. The Indian structural biology community has grown in the recent years and a large number of excellent scientific laboratories are active in this field in the country. India is planning to build synchrotrons in the future, but such an initiative requires about ten years for completion. Currently, scientific community of the country has limited, and geographically complicated access to the European Synchrotron Research Facility in Grenoble (France) and to Elettra in Trieste (Italy) through Indian investment at their (rather old) bending magnet beamlines. The Indian pharma industry does not have easy access of beamline, often commercial beamtime is purchased according to their needs. However, similar arrangement could be made at Australian synchrotron from Indian pharma companies or academic for accessing of the micro-focus beamline and fast data collection and analysis.

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