Drug Development

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 diffraction, which provides detailed structures of organic molecules such as drugs. We have a great deal of experience in drug development, so contact us today to see how we can help!

Arsenic Trioxide Rescues Structural p53 Mutations through a Cryptic Allosteric Site

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

Structure Basis for Inhibition of SARS-CoV-2 by the Feline Drug GC376

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

Structural Basis for Inhibition of the RNA-Dependent RNA Polymerase from SARS-CoV-2 by Remdesivir

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

Harnessing Calcineurin-FK506-FKBP12 Crystal Structures from Invasive Fungal Pathogens to Develop Antifungal Agents

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

Discovery of NV-5138, the First Selective Brain mTORC1 Activator

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

Trapping Biosynthetic Acyl-Enzyme Intermediates with Encoded 2,3-Diaminopropionic acid

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

Optimized Arylomycins are a New Class of Gram-Negative Antibiotics

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

Reactions of Neutral Cobalt(II) Complexes of a Dianionic Tetrapodal Pentadentate Ligand: Cobalt(III) Amides from Imido Radicals

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



Biomedical Imaging

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!

Investigating the Presence of Mercury under a Dental Restoration Using Synchrotron K-Edge Subtraction Imaging

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



Case Studies