A new spin to drug design
MAG-LAB leverages the power of NMR, enhanced by a unique set of protein isotope labeling techniques and decades of expertise in characterizing the driving forces of biomolecular interactions. These technologies are employed to evaluate drug-like molecules with atomic level precision
What we offer:
• Guidance for your hit-to-lead and subsequent lead optimization processes
• Complementation of your X-ray data or circumventing X-ray crystallography when determining small molecule binding sites/poses by combining NMR with computational methods
• Characterizing protein-ligand interactions in atomistic detail where the association happens: in solution
• Making the challenging “undruggable” targets of the proteome accessible
• Understanding the key mechanisms of how molecules interact
Our Mission
We offer in-depth interaction analysis of protein-ligand interfaces using:
NMR Spectroscopy:
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Atomic resolution
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Near physiological conditions
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Bound state dynamics
Isotope labeling:
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Highly selective
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Fully compatible with various expression systems
We support your medicinal chemistry campaign during:
Hit finding:
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Analysis of initial hits
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Selection of Promising Fragments
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Input for Compound Optimization
Hit-to-Lead Optimization:
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Binding mode analysis
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Input for Functional Group Modification and Fragment Merging
Isotope Labeling
Isoleucine
L01
L02
Methionine
L07
L08
Phenylalanine
R01
R03
R02
R11
We offer a unique portfolio of stable-isotope labeled small molecules to decorate proteins with deuterium, carbon-13 and/or nitrogen-15 at defined atomic positions
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fully compatible with routine minimal media E. coli overexpression
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minimal isotope scrambling
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high incorporation rates
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customized isotope labeling patterns available on demand
Valine and/or Leucine
L03
L05
L04
L06
Alanine
L09
L11
L10
L12
Tyrosine
R04
R05
Tryptophan
R07
R09
R08
R10
Selected research articles:
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T. Höfurthner, G. Toscano, G. Kontaxis, A, Beier, M. Mayer, L. Geist, DB. McConnell, H. Weinstabl, R. Lichtenecker*, R. Konrat, J. Biomol. NMR 2023
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G. Platzer, M. Mayer, A. Beier, S. Brueschweiler, J.E. Fuchs, H. Engelhardt, L. Geist, G. Bader, J. Schörghuber, R. Lichtenecker, B. Wolkerstorfer, D. Kessler, D.B. McConnell*, R. Konrat*, Angew. Chem. Int. Ed. 2020, 59, 14861-14868
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Schörghuber J, Geist L, Platzer G, Feichtinger M, Bisaccia M, Scheibelberger L, Weber F, Lichtenecker RJ* J Biomol NMR 2018, 71, 3, 129-140
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Schörghuber J, Geist L, Bisaccia M, Weber F, Konrat R, Lichtenecker RJ* J Biomol NMR 2017, 69, 1, 13-22
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Schörghuber J, Geist L, Platzer G, Konrat R, Lichtenecker RJ* ChemBioChem 2017, 18, 1487–1491
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Lichtenecker RJ*, Schörghuber J, Bisaccia M Synlett 2015, 26, 2611-2616
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Schörghuber J, Sara T, Bisaccia M, Schmid W, Konrat R, Lichtenecker RJ* ChemBioChem 2015, 16, 5, 746-751
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Lichtenecker RJ* Org. Biomol. Chem. 2014, 12, 7551-7560
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Lichtenecker RJ*, Weinhaeupl K, Schmid W, Konrat R, J. Biomol. NMR 2013 57(4): 327-331
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Lichtenecker RJ*, Weinhaeupl K, Reuther L, Schoerghuber J, Schmid W, Konrat R J. Biomol. NMR 2013 57(3): 205-209
Histidine
R06
R12
New in MAG-LAB:
We are constantly expanding our labeling methods to adapt isotope patterns to the needs of our partners and clients, as well as our in-house applications.
R13
R14
R15
R16
R17
NMR-guided drug development
MAG-LAB analyses your protein-ligand interface in atomistic detail using NMR to access information encoded in 1H nuclei
Assisted by the power of selective precursor labeling and NMR we analyse proteins and ligands in the bound state
We reveal a detailed picture of
non-covalent interactions as key factors for directed structure optimization
The four examples below will give you a first glimpse of MAG-LAB's tools and capabilities
#1 Examination of large protein targets
Protein: WDR5
Size: 34KDa
Sample concentration: 50µM
Measurement time: 30min
Selective labeling makes large proteins amenable for NMR characterization and significantly simplifies the spectral appearance of conventional 2D NMR spectra. This makes large protein targets accessible for fragment screening and binding site mapping approaches
Precursors R03, R05 and R10
Precursors L01and L05
MAG-LAB offers expression, purification, and labeling of your protein target
#2 Analysis of interaction surfaces
Selective protein labeling of Brd4-BD1 yields 2D-spectra with high resolution.
Ligand binding results in characteristic chemical shift perturbations, which can be linked to geometrical parameters of energetically favorable CH-π interactions.
Precursors R07 and R18
This work was supported by the Christian Doppler Laboratory of High-Content Structural Biology and Biotechnology and was published in Angew Chem Int Ed 2020, 59, 35, 14861
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Detection of π-Interactions in solution
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Applicable at fragment level (low affinities)
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Suitable for CH3, CH2 and CH donor groups
MAG-LAB offers customized isotope labeling patterns on request
#3 Ligand NMR signals as sensors for interaction
Valuable information is also contained in ligand chemical shifts. The binding of FKBP12 to the immunophilin GPI1046 is driven by multiple CH-π interactions of the pyrrolidine moiety with aromatic residues on the site of the protein. This interaction results in large chemical shifts (blue and red arrows) which are made visible using our ligand-detected approach.
ChemPhysChem 2024, 25(1), e202300636
#4 Targeting IDPs
Data-driven docking structure of a protein-small molecule complex
3RTau binding to a 3RT specific antibody
Protein-IDP complex structure solved by solution NMR
We offer a wide range of protein/ligand-based NMR experiments that employ tailored protein samples for your drug discovery projects.
Our NMR services include epitope mapping for antigen-antibody interactions, the elucidation of small-molecule binding sites, as well as the characterization of loosely folded or even intrinsically disordered proteins (IDPs)
ChemMedChem 2021, 16 (23), 3576-3587
Acta Neuropathologica 2018, 136, 69-87
Team
Wolfgang Friedl
CEO, Attorney at Law
Robert Konrat
Scientific head and Professor for Structural Biology at the University of Vienna
Sven Brüschweiler
Researcher (NMR and Structural Biology)
Katharina Siess
Researcher (Molecular Biology and Structural Biology)
Roman Lichtenecker
Researcher (Head of Organic Chemistry and Scientist at the University of Vienna)
Gerald Platzer
Researcher (NMR and Structural Biology)
Matus Hlavac
Researcher (Organic Chemistry)
Sarah Kratzwald
Master Student (Molecular Biology)
Alisa Wimmer
Master Student (Organic Synthesis)
Contact
A new spin to drug design
Contact us to learn more about the scope of protein labeling and biomolecular NMR spectroscopy. Become acquainted with the many ways MAG-LAB can endow your project with a new spin
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