Pharmaceuticals

• High-throughput protein crystallography with automated systems for drug discovery and drug optimisation applications.

• Characterising active pharmaceutical ingredients and formulations under simulated manufacturing conditions (e.g. pressure, ball milling, etc...).

• Characterising the structure and function of enzymes for drug development, including the location and movement of hydrogen atoms.

• In situ studies investigating how storage and transport conditions impact drug lifetime (e.g. accelerated ageing, humidity, temperature, UV exposure etc...).

• Revealing structural information about how drugs interact with therapeutic targets at the atomic level.

• Structural and interaction studies of colloid suspensions, micro-emulsions and micelles.

• Characterising the mechanisms of self-assembly in solutions.

• Solving solubility and stability issues for drug development and manufacturing.

• Studying aggregation and crystallisation phenomena.

• Detecting impurities.

• Polymorphism studies for protecting intellectual property and detecting patent infringement.

• Determining drug structure at the atomic level, including chirality, absolute configuration and identifying drug-molecule binding sites.

• Monitoring the penetration of drugs and pharmaceutical formulations into biological tissues such as the skin.

EXAMPLE

Neutron crystallography

Neutron crystallography allows the location and movement of hydrogen atoms to be determined. It can therefore reveal opportunities to enhance drug-binding and reduce drug resistance. Researchers used neutron crystallography to study HIV-1, an enzyme essential for the replication of the HIV virus. It revealed why the enzyme’s catalytic activity is pH sensitive which could help design new, more effective antiretroviral drugs.

EXAMPLE

AMPK (AMP-activated protein kinase)

AMPK (AMP-activated protein kinase) substrates are highly promising therapeutic drug targets for treating diabetes, cancer and ageing. Researchers at one of the world’s foremost drug discovery companies successfully solved the structure of AMPK at a resolution of 2.9 Ångstroms . This was enough for the researchers to see detailed information about the chemical environment in the AMPK binding site.

EXAMPLE

Microscopy

Using full-field transmission microscopy, researchers could create a 3D image of an entire cell infected with the hepatitis C virus (HCV) under almost physiological conditions . This revealed how the HCV virus causes structural alterations in the cell and how specific antivirals repair the cell. Such tools are extremely valuable for checking drug effectiveness and allow complex biological processes to be better understood.