ASTRAZENECA PLC
The study describes a novel method to directly extract membrane proteins from cells into lipid Salipro nanoparticles, enabling structure-function analysis using surface plasmon resonance (SPR) and cryo-electron microscopy (cryo-EM) for challenging drug targets. For this study, the teams leveraged GeneArt Gene-to-Protein Services, part of
The scientists extracted and purified functional membrane proteins directly from cells using the membrane protein PANX1 as a case study. PANX1 is associated with various pathologies, including inflammation, pain, ischemia, and epilepsy. Exploration of PANX1 as a potential therapeutic target for novel therapeutics has however been limited due to overall lack of biophysical studies using isolated systems.
'Analyzing membrane proteins using SPR can pose a challenge due to the inherent instability of these drug targets and the difficulty in immobilizing enough functional membrane protein on the biosensor surface to ensure a measurable binding signal. By employing this innovative technique, we were able to confirm target engagement and measure the binding affinities of various pharmacological agents that are known to inhibit PANX1 activity.' commented
'These results provide the basis for further investigations of novel PANX1 binders, leading to the development of more potent and specific compounds to further probe the biology of PANX1 and its potential as a therapeutic target. The novel methodology presented here accelerates the purification of membrane proteins that are ready to generate high-resolution cryo-EM structures, without the need for laborious and time-consuming detergent screenings, protein engineering or inefficient screening of alternative scaffolding setups.' said
'We are excited to see the synergies of our collaboration come together, enabling the first structure-function studies of this drug target and laying the groundwork for future investigations of novel PANX1 binders.' said
About
The majority of drug targets are so-called membrane proteins; however, these targets are inherently unstable and challenging to investigate. The proprietary Salipro technology stabilizes membrane proteins in their native forms, enabling them to be employed in drug discovery programs for therapeutic antibodies, small molecule drugs and structure-based drug design.
To date, Salipro Biotech has signed multiple research collaborations with top-tier pharma and biotech companies. Through in-house and partnered pipelines,
Contact:
Tel: +46 (0)72 939 5018
Email: maria.knudsen@salipro.com
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