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Industrial Liaison Group:
Tel: +44 (0) 1235 778797
E-mail: [email protected]
On the 8th to 10th November 2015 Claire Pizzey and Alexandre Dias from the Industrial Liaison team attended the PSDI 2015 Protein Structure Determination in Industry conference in Munich. Held at the Hotel Althoff Seehotel in Tegernsee, the conference brought together academic and industrial experts in the field of protein structure determination to discuss current topic such as the use of structures in Medicinal Chemistry, binding kinetics in drug discovery, structural studies on epigenetic targets, biopharmaceuticals, crystallization / crystal treatment & data collection, incl. high-throughput approaches and automation stories, and X-FEL as well as looking at new structures and hot targets.
Among the speakers at PSDI2015 were Isabel Moraes from the Membrane Protein Laboratory at Diamond Light Source who discussed recent developments made at the MPL/Diamond to tackle structure determination of membrane proteins.
Matthias Frech from Merck Serono presented the findings from the transeuropean collaborative project kinetics for drug discovery, k4dd. Focusing on hsp90 as a model, the aim of the propject was to investigate how kinetics can inform drug discovery.
In the second session concerned with Computational Chemistry, Biostructures and Biophysics, Lars Neumann from Proteros Biostructures GmbH based on Germany provided great insights in the lead identification of compounds binding to cdk8/cyccC via fragment screening and the effect of fragment extension on residence time and Simon Holton demonstrated how Bayer had developped Bay598 a new chemical probe for smyd2 thanks to their biophysics platform.
The second day of talks covered the use of structures in medicinal chemistry and biopharmaceuticals and Alex Milbradt from AstraZeneca spoke about Fragment based discovery of the first known inhibitor of PHGDH which is implicated in agressive breast cancer.
Martina Schafer from Bayer gave a presentation on the discovery of BAY 85-8501, a Novel and Highly Potent Induced-Fit Binder of Human Neutrophil Elastase for Pulmonary Diseases and David Hargreaves from AstraZeneca talked to delegates about how antibody assisted crystallisation and structural information (Novel Mcl-1 Antibody Assisted Crystal System) helped AstraZeneca optimise hits via DNA encoded library screening.
Closing the second and final day of the talk programme was the session on biopharmaceuticals. Topics in this session included discussions on structural biology in vaccine research and structural based antibody engineering.
Claire Pizzey from the Diamond Industrial Liaison team comments.
"PSDI 2015 was a very interesting conference in a great location. It's a really good opportunity for industrial scientists hear about the latest developments in MX and crystallisation and learn about the newest techniques for structural biology. It's also an excellent chance for us to gain insight into the specific areas of interest for industrial scientists working in structural biology to enable us to develop our capabilities and services."
"Diamond was well represented at the meeting with Frank von Delft giving an overview of the fragment screening platform currently under development and Isabel Moraes highlighting the opportunities available at the Membrane Protein Lab. Of course one of the main goals for the meeting is networking and it was great to meet friends old and new while enjoying the 5* facilities and beautiful views of Lake Tegernsee."
The COVID-19 virus pandemic caused by the SARS-CoV-2 coronavirus poses an ongoing serious global health threat that requires effective and safe therapeutics. The SARS-CoV-2 coronavirus uses its spike glycoprotein to bind to the host receptor angiotensin-converting enzyme-2 (ACE-2) and enter the body’s cells.
The receptor-binding domain (RBD) of the spike glycoprotein is the main target for neutralising antibodies as it can block the virus-host interaction and prevent the infection. The RBD is highly variable and can mutate to escape recognition by antibodies, thus reducing their efficacy and increasing the risk of resistance.
Moreover, the RBD is only exposed transiently on the spike glycoprotein, making it difficult for antibodies to access and bind to it. Novel antibodies are needed that can recognise and neutralise the RBD of SARS-CoV-2 with high potency and stability, regardless of its variability and accessibility
Read more...The ability to modulate drug delivery at therapeutically effective doses over a sustained period of time, in vivo, is very challenging. In the case of poorly water-soluble drugs this requires a carefully designed matrix to manage and maintain their controlled release.
Lipid cubic phase carriers offer an effective way to transport both small molecules and larger proteins through oral and parenteral routes (those outside of the digestive tract), as well as local delivery via subcutaneous and intramuscular routes. Complex interactions between the drug and the lipid matrix govern the release profile; for hydrophilic drugs, release can be very fast. The carriers can also be compromised by naturally occurring lipolytic enzymes which act to break down the lipid microstructure.
Read more...With 27% of global energy consumption occurring in the residential sector, harvesting and storing thermal energy is increasingly important.
A promising technology is based on phase-change materials (PCMs) that absorb or release large amounts of heat when they change state, e.g. from solid to liquid.
PCMs incorporated into building materials could remove excess heat during the day and release it at night, with minimum carbon emissions. One approach in stabilising PCMs for use is nanoscale confinement in core-shell structures.
Medicinal products extracted from biological sources, called biopharmaceuticals or biologics, must be carefully produced to ensure that only high purity active material is generated. Biopharmaceutical manufacturing processes can have an impact on the amount of product-related variants in the final clinical material. Understanding and controlling amounts of these product-related variants is a major challenge in the development of biopharmaceutical products.
Read more...Elastin allows tissues in humans and other mammals to stretch and return to original shape e.g. during respiration or heart beats. The schematic on the right shows how many tropoelastin monomers (blue) can selfassemble and cross-link (red) to form elastin but the structure of the soluble precursor of elastin, tropoelastin, is not well understood.
Read more...Diamond Light Source is the UK's national synchrotron science facility, located at the Harwell Science and Innovation Campus in Oxfordshire.
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