Tuesday, March 14, 2006, 10:30 am — Seminar Room, Bldg. 725
Numerous academic institutions and pharmaceutical/biotechnology companies have been developing high-throughput techniques for protein crystallography during the past few years. Takeda San Diego, Inc. (formerly Syrrx, Inc.) has a highly automated gene-to-structure platform in place, which includes its proprietary Nanovolume Crystallization(r) Technology and an automated beamline at the Advanced Light Source. This platform has enabled our scientists to carry out almost 10 million crystallization trials, harvest and screen (with x-rays) approx. 15000 crystals, collect over 1500 datasets and obtain hundreds of crystal structures. Tight integration of structural information with chemistry led to the development of several pre-clinical candidates and compounds which are now in clinical trials. In the case of the Dipeptidyl Peptidase 4 enzyme, which is a drug target for Type II diabetes and obesity, an IND was filed only 2 years after the first DP4 crystal structure was solved. An overview of the automated process at Takeda San Diego, Inc., from protein crystallization to structure determination, as well as a statistical overview of its performance to date will be presented. Some highlights of our published research will be also shown. Our results show, that structure-based drug discovery works very well in practice and that a highly automated platform can significantly accelerate the process of obtaining de-novo crystal structures and co-complexes from the selection of an initial protein target. Meticulous database-oriented record keeping and collaboration across several departments and several fields is necessary to make it work.
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