caa a22 4500 477126693 CHVBK 20180405111651.0 cr unu---uuuuu 170330e19971201xx s 000 0 eng 10.1023/A:1012123628123 doi (NATIONALLICENCE)springer-10.1023/A:1012123628123 Study of the Complex Between the Contrast Agent lobitridol (Xenetix®) and Elastase (PPE): A Model for Hydrophobic Site Protection in Drug-Protein Interactions [Elektronische Daten] [Thierry Prangé, Alain Neuman, Claire Corot, Dominique Meyer] Purpose. The concept of Hydrophilic Sphere Stabilization, or Hydrophobic Shielding, has been postulated in the synthesis of biocompatible contrast agents in vascular imaging. To improve the safety of these polyiodinated agents, interactions with protein hydrophobic sites in biomacromolecules should be kept as low as possible. In order to evaluate the level of interactions with proteins, we have selected the serine proteinase Elastase, in presence of Iobitridol (Xenetix®), as a model. Methods. The complex between Iobitridol and Pancreatic Porcine Elastase was investigated by X-ray diffraction techniques, on saturated monocrystals, using the synchrotron radiation at 0.98Å. Results. In contrast to Iohexol, which displays several interactions including one in the active site, Iobitridol is unable to interact directly with elastase. Only one partially occupied site is found in between two molecules of the crystal packing. Conclusions. The validation of the 'hydrophobic shielding' concept, which was at the origin of the design of the Iobitridol molecule, has been proven to be an essential feature in minimizing in vivo protein interactions. Plenum Publishing Corporation, 1997 iobitridol nationallicence proteinase nationallicence hydrophobic shielding nationallicence contrast agent nationallicence X-ray diffraction nationallicence Prangé Thierry Chimie Structural Biomoleculaire (URA-1430 CNRS) F-93017, Bobigny Cedex, France aut Neuman Alain Chimie Structural Biomoleculaire (URA-1430 CNRS) F-93017, Bobigny Cedex, France aut Corot Claire GCA Service Immuno-Hemato-Biochimie, Z.A. De 1'Islon F-38670 Châsse sur Rhône, France aut Meyer Dominique GCA Service Immuno-Hemato-Biochimie, Z.A. De 1'Islon F-38670 Châsse sur Rhône, France aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/12(1997-12-01), 1713-1717 0724-8741 14:12<1713 1997 14 11095 https://doi.org/10.1023/A:1012123628123 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012123628123 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Prangé Thierry Chimie Structural Biomoleculaire (URA-1430 CNRS) F-93017, Bobigny Cedex, France aut NATIONALLICENCE 700 1- Neuman Alain Chimie Structural Biomoleculaire (URA-1430 CNRS) F-93017, Bobigny Cedex, France aut NATIONALLICENCE 700 1- Corot Claire GCA Service Immuno-Hemato-Biochimie, Z.A. De 1'Islon F-38670 Châsse sur Rhône, France aut NATIONALLICENCE 700 1- Meyer Dominique GCA Service Immuno-Hemato-Biochimie, Z.A. De 1'Islon F-38670 Châsse sur Rhône, France aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/12(1997-12-01), 1713-1717 0724-8741 14:12<1713 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer