New routes for magnetic resonance spectroscopy of biomolecules by combining EPR and NMR methods

Detection of magnetic nuclei via magnetic resonance spectroscopy (NMR/EPR) or imaging (MRI) is one of the most important tools to achieve structural and functional information in natural sciences.

Latest developments in this field are taking advantage of the larger (about three orders of magnitude) spin polarization of unpaired electrons in paramagnetic molecules to tremendously enhance the sensitivity of nuclear magnetic resonance. However, most protocols still suffer from several bottlenecks and lack of general applicability to bio-macromolecules.

This proposal aims at expanding electron-nuclear spin polarization transfer to develop new magnetic resonance tools: 1) EPR-based nuclear spin detection for structural information in the angstrom-to-nanometer scale and 2) hyperpolarized high-field NMR in the liquid state.

Research in these two directions will take advantage from concerted investigations of polarization transfer mechanisms and their representative applications to biomolecular systems.

Reaching this goal will permit new studies, not feasible with current techniques, for instance understanding the molecular mechanism of enzyme activation, subunits interactions and inhibition in ribonucleotide reductases, which are important targets of cancer drugs.

Our laboratory possesses suited expertise and a state-of-the art combination of EPR and NMR instrumentation, by which these questions can be tackled in synergy.

The research program encompasses a variety of investigations, from new experimental and instrumental designs up to short and long-term potential applications in biomolecules, for instance in the investigations of enzyme interactions with drugs, which are currently hampered by low sensitivity and resolution.

A successful establishment, combined with current progress in magnetic resonance instrumentation, i.e. the age of magnetic resonance in GHz (NMR) and THz (EPR), will offer new opportunities for analytical and biophysical investigations.