POWRE: Molecular Mechanisms of Binding of Gd(3+) Complexes to Biomolecules

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SmirnovaMCB 0075042The aim of this research is to understand molecular mechanisms of reversible binding of paramagnetic contrast agents (PCA's) developed for Magnetic Resonance Imaging (MRI) to biological macromolecules, phospholipids and proteins, and the effort of these interactions on relaxivity of PCA's. Contrast-enhanced MRI has wide applications in clinical work and is a powerful tool in research. New applications are emerging in microimaging and developmental biology. However not enough is known about structure-function relationships of PCS's, especially the molecular mechanisms of reversible binding of PCA to biological macromolecules, and the effects of biological environment on relaxivity of PCA's. This research will characterize the binding interactions and investigate the effect of these interactions on relaxivity of PCA's through systematic studies of a series of lanthanide ion complexes (Gd(III) with different lipophilicity by a combination of spectoscopic techniques, including fluorescence, nuclear magnetic resonance, and electron magnetic resonance at multiple and high magnetic fields. Model phospholipids will be used to see how lipophilicity affects the ability of PCA's to interact non-specifically with biological membranes and how these interactions change relaxivity of the Gd(III) complex. PCA non covalent binding with human serum albumin will use a combination of spin-labeling EPR, fluorescence, and HF EPR to map the PCA binding sites over the albumin molecule and to study how changes in lipophilicity of these complexes affects the binding. Fatty acid binding proteins, which have a single but very different binding site than albumin will also be examined. This is a POWRE proposal, which will allow the PI who is trained as a physical chemist to extend her skills into molecular biology.