Native nanoESI-MS, FAXS Fluorine chemical shift Anisotropy and eXchange for Screening and DOSY Diffusion Ordered Spectroscopy.
This specific application of MS is called supramolecular-, noncovalent-, nondenaturing- or native-MS. This approach is used for the detailed structural and functional characterisation of a wide variety of assemblies consisting of several proteins, proteins and small molecules, nucleic acids, proteins and nucleic acids, as well as nucleic acids and small molecules.
The main strengths of native MS include:
As a consequence, two major applications for native MS have emerged rapidly:
Ref: Vivat el al., Future med Chem.,1(2), Jan 2010, pp.35-50(16). Renaud and Delsuc, Curr. Op. Pharmacol., 9(5), Oct 2009, pp 622-628(9).
The ligand- and substrate-based fluorine NMR approaches are powerful tools for rapidly performing screening against a biomolecular target and determining the KD and IC50 values of the identified hits.
The use of 19F chemical-shift mapping studies to study ligand binding has several advantages:
As well as the ability to detect weak intermolecular interactions makes NMR ideal for fragment-based screening.
Ref: Dalvit, Ligand – and substrate-based 19F NMR screening: Principles and applications to drug discovery; Progress Nuc. Reson. Magn. (2007) pp 243-271. Bartoli et al., The fragment-approach: An update; Drug Discovery: Technologies (2006) pp425-431.
NMR diffusion experiments provide a way to separate the different compounds in a mixture based on the differing translation diffusion coefficients (and therefore differences in the size and shape of the molecule, as well as physical properties of the surrounding environment such as viscosity, temperature, etc) of each chemical species in solution.
In a certain way, it can be regarded as a special chromatographic method for physical component separation, but unlike those techniques, it does not require any particular sample preparation or chromatographic method optimization and maintains the innate chemical environment of the sample during analysis.
NovAliX studies are enabled and powered by a powerful proprietary software for NMR data processing and management for rapid and efficient analysis.
Ref: Assemat et al. Validation of molecular mass measurements by means of Diffusion-Ordered NMR Spectroscopy; Application to Oligosaccharides. CRChimie (2009) pp. 1-8. Balayssac et al. 2D and 3D DOSY 1H NMR, a useful tool for analysis of complex mixtures: Application to herbal drugs or dietary supplements for erectile dysfunction. Journal of Pharmaceutical and Biomedical Analysis (2009) vol. 50 pp. 602-612. Arold et al. Characterization and molecular basis of the oligomeric structure of HIV-1 nef protein. Prot Science (2000) vol. 9 (6) pp. 1137-48. Delsuc and Malliavin. Maximum entropy processing of DOSY NMR spectra. Anal Chem (1998).