STUDY OF THE COMPLEX BETWEEN THE CONTRAST AGENT IOBITRIDOL (XENETIX(R)) AND ELASTASE (PPE) - A MODEL FOR HYDROPHOBIC SITE PROTECTION IN DRUG-PROTEIN INTERACTIONS

Purpose. The concept of Hydrophilic Sphere Stabilization, or Hydrophob ic Shielding, has been postulated in the synthesis of biocompatible co ntrast agents in vascular imaging. To improve the safety of these poly iodinated agents, interactions with protein hydrophobic sites in bioma cromolecules should be kept as low as possible. In order to evaluate t he level of interactions with proteins, we have selected the serine pr oteinase Elastase, in presence of Iobitridol (Xenetix(R)), as a model. Methods, The complex between Iobitridol and Pancreatic Porcine Elasta se was investigated by X-ray diffraction techniques, on saturated mono crystals, using the synchrotron radiation at 0.98 Angstrom. Results, I n contrast to Iohexol, which displays several interactions including o ne in the active site, Iobitridol is unable to interact directly with elastase. Only one partially occupied site is found in between two mol ecules of the crystal packing. Conclusions. The validation of the ''hy drophobic shielding'' concept, which was at the origin of the design o f the Iobitridol molecule, has been proven to be an essential feature in minimizing in vivo protein interactions.