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Nuclear Magnetic Resonance (NMR) spectroscopy is a very powerful tool for drug discovery. Our facility consists of four high-resolution solution state-of-the-art Bruker spectrometers, including two 600 MHz, one 500 MHz and one 400 MHz, that can support your project with:

  • Structural, purity, solubility, and chemical stability assessment of small molecules
  • Analysis of the oligomerization state of peptides and proteins
  • Determination of macromolecule 3D structure and conformational dynamics
  • Protein-ligand and protein-protein interaction studies
  • Fragment screening, hit validation and lead optimization

Our NMR Team excels in leveraging this technology across a wide range of applications, delving into the 3D structure and dynamic properties of biomolecules, ranging from small peptides to large proteins and protein complexes. Additionally, we employ Fragment-Based Drug Discovery (FBDD) and conduct structure-activity relationship (SAR) analyses to identify and advance hits in the early stages of drug discovery.

Biomolecular 3D structure and dynamics

NMR can be used to understand the 3D structure and dynamics of biomolecules in solution under different conditions that mimic their physiological environment.

We can use this technique to study biomolecules, from small peptides to large proteins and protein complexes that we can readily produce in house with the appropriate isotopic labeling.

Once obtained, the structural/dynamic information is then used to identify best druggable sites and to allow the investigation of ligand-protein/protein-protein interactions.

NMR is highly complementary to X-ray crystallography and is unique in enabling the investigation of structural features of challenging drug targets such as transmembrane receptors and intrinsically disordered proteins. In the case of therapeutic peptides, it can also guide the SAR by determining the structural propensity, solvent accessibility, and local flexibility of each residue with atomic resolution.

Oligomerization state analysis

Particularly in the field of therapeutic peptides, the solution state of a molecule can define its bioavailability and metabolic stability.

In our NMR group, we can screen the propensity of drug candidates to oligomerize or aggregate in near-physiological conditions, and at dosing solution concentrations.

NMR offers a robust and quick response, when characterizing the size of the soluble oligomers and providing insights on the aggregation mechanism. This type of information is extremely important for guiding further optimization of the peptide and identifying a convenient formulation of the drug candidate.

Fragment screening and hit validation

Fragment-based Drug Discovery (FBDD) is a very popular strategy to develop hits in the early phases of drug discovery.

We use a variety of NMR methods to screen fragment libraries for binding to defined target biomolecules, thus generating initial low-affinity hits that can be used to jumpstart fragment-based drug discovery projects.

NMR can also be used to validate hits from other screens such as high throughput and virtual screens.

Hit to lead and lead optimization

NMR-based methods can help ranking hits according to affinity and identifying ligands that bind to the target in close proximity, offering valuable insights into how to properly grow and merge fragment hits.

SAR by NMR is then applied to structurally analyze the ligand-target complex, both in terms of binding site and binding mode, thus providing essential information for structure-based optimization and medicinal chemistry during the lead optimization phase.







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