NMR is the gold standard for sorting out binding behaviors and can immediately allow modeling of the docked ligand, which is very helpful for planning a chemistry optimization strategy. NMR can provide detailed structures of peptides and macrocycles, that is molecules that generally do not crystallize. These detailed structures guide the design of analogs that are more potent, more stable, and/or more bioavailable. The sophisticated NMR techniques needed to deal with macromolecules can be applied to smaller molecules to answer complex questions of structure or stereochemistry, or to provide the most rigorous proof of structure.
NJ Bio’s NMR services include:
- Verification of screening hits; definition of binding location(s).
- NMR screening of fragment libraries to obtain leads and Targeted Protein Degrader (TPD) ligands
- Full detailed structures of proteins, protein-ligand complexes, peptides, macrocycles, oligonucleotides, and antisense molecules.
- Advanced NMR methods to determine and verify small molecule structures.
NMR is the “Gold Standard” Method for Hit Validation.
black = only protein; red = protein + compound.
Binding is validated. Key residues are identified.
Example: Mapping of key residues (on Interleukin-2 structure) indicates binding site.
NJ Bio has a dedicated 500-MHz NMR spectrometer that is optimized for all modern 2D and 3D 1H, 13C, and 15N experiments on macromolecules.