Press Release (ePRNews.com) - VILLIGEN, Switzerland - Jun 03, 2018 - leadXpro and the University of Zurich (UZH) collaborate to generate sybodies as molecular discovery tools, therapeutic lead compounds and diagnostic reagents against disease-relevant membrane protein targets.
Membrane proteins such as transporters, ion-channels and GPCR’s are therapeutic targets for highly successful medicines. leadXpro has deep expertise in the generation of membrane protein samples for biophysical analysis and structural investigation by X-ray crystallography and cryo-electron microscopy. leadXpro generates and applies such samples to the discovery and optimization of small molecule and biotherapeutic lead compounds. This will extend drug discovery options for previously intractable or challenging membrane protein drug targets.
Under this research and development collaboration, leadXpro provides purified membrane protein and UZH applies their sybody platform, which is unique in generating synthetic single-domain antibodies, termed sybodies, against challenging membrane proteins. leadXpro has the option to acquire any resulting commercial applications of the developed products. The collaboration is supported by the grant 25864.1 PFLS-LS from the Swiss Innovation Agency Innosuisse.
This collaboration is our first entry into the biologics discovery space.
Mathieu Botte (Senior scientist and project leader at leadXpro) remarked: “Generation of high-quality membrane protein samples is a core competence of leadXpro’s lead discovery platform. Within only three weeks, our collaboration partners at UZH have successfully generated a highly diverse set of sybodies that are directed against our challenging target protein. Binding properties were characterized with our platform of biophysical methods (e.g. wave guided interferometry) and revealed up to pM affinities and favorably slow dissociation rates for several binders. Sybodies are therefore ideal candidates for the formation of stable complexes for structural studies and they represent excellent therapeutic lead compounds.”
Markus Seeger (project leader and Professor at UZH) said: “In this challenging project, we apply our recently developed sybody selection platform to enable drug discovery on a disease-relevant membrane protein. As an academic innovator lab, we have a strong interest in making our technology accessible to skilled and experienced industry partners, like leadXpro.” Iwan Zimmermann (co-inventor of the Sybody technology, UZH) added: “The project gained quickly momentum, due to the combination of the excellent target quality delivered by leadXpro and our highly efficient sybody platform. The collaboration is an excellent validation of our binder technology towards future therapeutic applications.”
Michael Hennig added: “In addition to employing our membrane protein samples for our biophysical and structure-based analytical tool set, we can now expand the utility of our samples as antigens for the generation of sybodies or antibodies. While this collaboration is our first entry into the biologics discovery space, benefits from the generated sybodies as stabilization, crystallization and tools to aid our structure guided small molecule platform are also very welcome and contribute additional value to our existing membrane protein generation platform.”
Sybodies are synthetic single domain antibodies that have been developed in the research group of Markus Seeger at UZH. Sybodies have been engineered for targeting challenging integral membrane proteins and are selected entirely in vitro, thereby enabling rapid binder generation in the presence of non-covalent ligands against delicate targets. Due to their high thermal stabilities and low production costs, sybodies show promise for diagnostic as well as therapeutic applications. Sybodies are ideally suited to trap intrinsically flexible membrane proteins in defined conformational states and thereby facilitate structure determination by X-ray crystallography and cryo-EM.
More information on sybodies can be found in a recent paper of the Seeger group: https://elifesciences.org/articles/34317
About University of Zurich
The University of Zurich (UZH) is a member of the League of European Research Universities and numbers among Europe’s most prestigious research institutions. UZH’s international standing is reflected in the many renowned academic distinctions conferred upon its members, including twelve Nobel Prizes. As Switzerland’s largest university, UZH has a current enrollment of over 26,000 students and offers the most comprehensive academic program in the country. Over 5,000 excellent members of staff teach and perform research at one of the University’s 150 departments, including over 500 professors. UZH also looks back on a rich history, having been founded in 1833 as Europe’s first university to be established by a democratic political System. The research group of Markus Seeger is located at the Institute of Medical Microbiology. For more information please visit www.uzh.ch and http://www.imm.uzh.ch/de/research/experimental/teamseeger.html.
About leadXpro AG
leadXpro is a lead discovery company focusing on membrane protein drug targets. We are committed to the application of biophysical and structure-based methods for the discovery and optimization of next generation lead compounds. leadXpro’s technology platform enables structural determination of membrane proteins where classical crystallographic techniques fail, unlocking structure-based drug discovery for challenging targets. We capitalize on the knowledge regarding membrane protein structural biology and facilities of the Paul Scherrer Institute (PSI) with premium access to the Synchrotron Swiss Light Source (SLS) and the Free Electron Laser (SwissFEL). Core expertise beyond X-ray includes single particle cryo-electron microscopy (cryo-EM) and electron diffraction (ED). For more information, please visit www.leadxpro.com.
leadXpro is a registered trademark in the EU, Switzerland, US and Canada.