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Nuclear Magnetic Resonance (NMR)
Ichor has priority access to the NMR facilities and high-field instrumentation necessary to collect your FDA required biosimilar comparability data or to conduct a high-throughput fragment screen. With project management and bolt-on consulting and data analysis services, Ichor offers fast turnaround times to make your deadlines, in addition to personalized, attentive, and thoughtful collaboration for custom experiments and pulse sequences
What is NMR Spectroscopy?
Nuclear Magnetic Resonance (NMR) is a physical phenomenon in which nuclei in a strong constant magnetic field are perturbed by a weak oscillating magnetic field (i.e. a radio frequency pulse) and respond by producing an electromagnetic signal with a frequency characteristic of the magnetic field at the nucleus. This effect only occurs on certain NMR active nuclei, such as 1H, 13C, 15N, and 19F, readily lending the technique to analysis of biomolecules and organic small molecules. The response of each nuclei is exquisitely sensitive to its surrounding chemical environment, allowing it to report not only on chemical bonds but also the proximity, folding state, and aqueous environment of amino acid residues in proteins or nucleobases in RNA. NMR analysis can be conducted on samples with natural isotopic abundance as well as samples enriched in NMR active nuclei.
NMR spectroscopy encompasses a wide range of applications:
Small Molecule CMC: NMR allows for rapid assessment of the identity and purity of small molecules.
Drug Discovery: There are numerous NMR based approaches to small molecule drug discovery, including various protein-observed and ligand-observed NMR experiments.
Biosimilar Comparability: 2D 1H-15N and 1H-13C “fingerprint” spectra can be overlaid and statistically analyzed to quantitatively determine the batch-to-batch comparability of biosimilars like antibody therapeutics.
Protein Sequence, Structure, and Dynamics: Determine the backbone amino acid sequence, 3D structure, and solution-phase conformations of proteins, providing insight into protein function and interactions with other molecules.
Our NMR Services and Capabilities:
Our NMR services include 1H and 19F binding assays for high-throughput compound screening (FAXS, STD-NMR, WaterLOGSY), in addition to various 2D correlation experiments such as 1H-1H (COSY, NOESY, ROESY), 1H-15N (SOFAST-HMQC) and 1H-13C (ALSOFAST-HMQC) correlation spectroscopy.
Protein experiments are typically conducted on an 800 MHz NMR system equipped with a triple resonance TCI cryoprobe (1H, 13C, & 15N channels). This system is sensitive enough to allow for experiments with natural abundance biomolecules, such as drug formulations. For compound screening experiments, we typically use a 600 MHz NMR system equipped with a dual channel BBFO probe that can be tuned to both 1H and various X-nuclei, such as 19F. Multiple instruments are equipped with SampleJet robots allowing for low volume and high-throughput screening formats. Also offered are services for production of isotopically enriched recombinant proteins.
Popular FBDD and Biosimilar NMR Services
Ichor offers all the cutting-edge NMR experiments for Fragment-Based Drug Discovery and Biosimilar Comparability.
WaterLOGSY
A sensitive ligand-observed NMR experiment for detection of interactions between a ligand and a protein; well-established screening technique for FBDD and complement to STD-NMR
Data Acquisition
Ichor offers various 1D and 2D NMR experiments from everything from small molecules to antibodies and other complex biologics:
Simple 1D experiments are available for everything from small molecule and protein QC to HTS screening (FAXS, STD-NMR, waterLOGSY).
Two dimensional 1H-15N experiments are commonly used for both protein QC (fingerprinting coupled with PCA or Mahalanobis Distance calculations), as well as various protein-protein and protein-ligand binding experiments & titrations.
Available Spectrometers (priority access):
- 500 MHz (1)
- 600 MHz (2)
- 800 MHz (1)
All equipped with triple resonance TCI CryoProbes (1H,13C,15N) for fast, high-quality data collection.
Various multidimensional correlation experiments are also available. Custom pulse sequences can be developed upon request.
Two dimensional 1H-13C experiments are another commonly used technique for fingerprinting and QCing large biomolecules, including antibodies. Ichor offers isotopically enriched recombinant protein expression (2H, 13C, & 15N).
Options to facilitate screening:
- SampleJet robots (automation)
- 96-well plate format
- Low volume (65 µL)
- Temperature control
Add-On Services to Supply Your Entire Pipeline:
Production of Isotopically Enriched Recombinant Proteins
We offer recombinant protein production (E. coli and insect) with heavy isotope incorporation (2H, 13C, & 15N). Please inquire about discounts for bundling in-house protein production services with our analytical offerings.
Consulting & Data Analysis
For more complex, nuanced, or data intensive projects, NMR specialists are available for hourly consultation.
