Drug development and protein crystallography are one of the core applications of synchrotron facilities.
The primary technique used by our pharmaceutical clients is macromolecular crystallography (MX). MX provides detailed protein structures at angstrom-level spatial precision. Knowing the exact structures of target proteins and enzymes allows for the rational design of drugs and cofactors that interact with the active sites of target macromolecules. Aside from MX, we also offer analytical services for small molecule and powder X-ray diffraction (PXRD), which can provide detailed structures of organic molecules, including pharmaceuticals. Synchrotron techniques can provide an important technical basis for creating pharmaceutical intellectual property (IP), and can be critical for determining the outcome of patent litigation. We have provided patent litigation and IP consulting services, and have a great deal of experience in drug development, so contact us today to see how we can help!
Chen, Shuo; Wu, Jia-Le; Liang, Ying; Tang, Yi-Gang; Song, Hua-Xin; Wu, Li-Li; Xing, Yang-Fei; Yan, Ni; Li, Yun-Tong; Wang, Zheng-Yuan; Xiao, Shu-Jun; Lu, Xin; Chen, Sai-Juan and Lu, Min. (2021). Arsenic trioxide rescues structural p53 mutations through a cryptic allosteric site. Cancer Cell 39(2), 225-239. 10.1016/j.ccell.2020.11.013
Luan, X.; Shang, W.; Wang, Y.; Yin, W.; Jiang, Y.; Feng, S.; Wang, Y.; Liu, M.; Zhou, R.; Zhang, Z.; Wang, F.; Cheng, W.; Gao, M.; Wang, H.; Wu, W.; Tian, R.; Tian, Z.; Jin, Y. Jiang, H.; Zhang, L.; Xu, H. and Zhang, S. (2020). Structure basis for inhibition of SARS-CoV-2 by the feline drug GC376. bioRxiv. 10.1101/2020.06.07.138677
Yin, W.; Mao, C.; Luan, X.; Shen, D.; Shen, Q.; Su, H.; Wang, X.; Zhou, F.; Zhao, W.; Gao, M.; Chang, S.; Xie, Y.; Tian, G.; Jiang, H.; Tao, S.; Shen, J.; Jiang, Y.; Jiang, H.; Xu, Y.; Zhang, S.; Zhang, Y. and Xu, H. (2020). Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesiver. Science 368(6498), 1499-1504. 10.1126/science.abc1560
Juvvadi, P.; Fox, D.; Bobay, B.; Hoy, M.; Gobeil, S.; Venters, R.; Chang, Z.; Lin, J.; Averette, A.; Cole, D.; Barrington, B.; Wheaton, J.; Ciofani, M.; Trzoss, M.; Li, X.; Lee, S.; Chen, Y.L.; Mutz, M.; Spicer, L. Schumacher, M.; Heitman, J. and Steinbach W. (2019). Harnessing calcineurin-FK506-FKBP12 crystal structures from invasive fungal pathogens to develop antifungal agents. Nature Communications 10, 4275. 10.1038/s41467-019-12199-1
Sengupta, S.; Giaime, E.; Narayan, S.; Hahm, S.; Howell, J.; O'Neill, D.; Vlasuk, G. and Saiah, E. (2019). Discovery of NV-5138, the first selective brain mTORC1 activator. Scientific Reports 9, 4107. 10.1038/s41598-019-40693-5
Huguenin-Dezot, N.; Alonzo, D.; Heberlig, G.; Mahesh, M.; Nguyen, D.; Dornan, M.; Boddy, C.; Schmeing, T. and Chin, J. (2018). Trapping biosynthetic acyl-enzyme intermediates with encoded 2,3-diaminopropionic acid. Nature 565, 112-117. 10.1038/s41586-018-0781-z
Smith, P.; Koehler, M.; Girgis, H.; Yan, D.; Chen, Y.; Chen, Y.; Crawford, J.; Durk, M.; Higuchi, R.; Kang, J.; Murray, J.; Paraselli, P.; Park, S.; Phung, W.; Quinn, J.; Roberts, T.; Rouge, L.; Schwarz, J.; Skippington, E.; Wai, J.; Xu, M.; Yu, Z.; Tan, M.W. and Heise, C. (2018). Optimized arylomycins are a new class of Gram-negative antibiotics. Nature 561, 189-194. 10.1038/s41586-018-0483-6
Nurdin, L.; Spasyuk, D.; Piers, W. and Maron, L. (2017). Reactions of neutral cobalt(II) complexes of a dianionic tetrapodal pentadentate ligand: Cobalt(III) amides from imido radicals. Inorganic Chemistry 56(7), 4157-4168. 10.1021/acs.inorgchem.7b00174
X-ray imaging is a staple of clinical and biomedical R&D. Synchrotron radiography and CT take X-ray imaging to a whole new level.
X-ray imaging is one of the most ubiquitous medical imaging tools available. Clinical X-ray imaging can only be used for high-contrast systems such as bone/tissue or heavy-element contrast agents, and the images are typically low-resolution (with pixels on the scale of mm). Synchrotron X-ray imaging offers significantly higher contrast, allowing for the imaging of soft tissue like organs, vasculature, and tumors - often without the need for a contrast agent. Synchrotron CT is also considerably faster, allowing for micron-level imaging at high speed (often whole CT scans can be collected in a matter of seconds). This is especially useful for in-vivo and in-situ applications. Industrial applications include medical implants, research animals, excised tissues, dental structures and much more!
Hedayat, Assem; Belev, George; Zhu, Ning; Bond, Toby and Cooper, David. (2018). Investigating the presence of mercury under a dental restoration using synchrotron K-edge subtraction imaging. Microscopy and Microanalysis, 24(2), 362-363. 10.1017/S1431927618014101