Solution structure of the supramolecular adduct between a liver cytosolic bile acid binding protein and a bile acid-based gadolinium(III)-chelate, a potential hepatospecific magnetic resonance imaging contrast agent.

Bile acid-conjugated gadolinium chelates were shown to display promising features for the development of hepatospecific constrast agents for magnetic resonance imaging (MRI). The study of the pharmacokinetics of these compounds should address their possible interaction with the bile acid protein transporters. We have previously shown that a 5beta-cholanoic acid-based contrast agent is efficiently internalized in hepatocytes and is able to bind to a liver bile acid binding protein (BABP) in vitro. Here we report the solution structure of the adduct between a BABP and a gadolinium chelate/bile acid conjugate. The identification of unambiguous intermolecular distance restraints was possible through 3D edited/filtered NOESY-HSQC experiments, together with distance information derived from paramagnetic relaxation enhancements. These intermolecular contacts were used for the structure determination of the complex, using the data-driven docking software HADDOCK. The obtained results represent the starting point for the design of new and more efficient MRI contrast agents.