Literature DB >> 9453058

Study of the complex between the contrast agent Iobitridol (Xenetix) and Elastase (PPE): a model for hydrophobic site protection in drug-protein interactions.

T Prangé1, A Neuman, C Corot, D Meyer.   

Abstract

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 0.98A.
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.

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Year:  1997        PMID: 9453058     DOI: 10.1023/a:1012123628123

Source DB:  PubMed          Journal:  Pharm Res        ISSN: 0724-8741            Impact factor:   4.200


  25 in total

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Journal:  Nature       Date:  1994-02-17       Impact factor: 49.962

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Authors:  A Morton; B W Matthews
Journal:  Biochemistry       Date:  1995-07-11       Impact factor: 3.162

5.  Angiography contrast agents interact with serine proteinases. The molecular structure of the model system elastase/iohexol.

Authors:  T Prangé; F Gaudey; J Ohanessian; D Avenel; A Neuman; C Corot; D Meyer
Journal:  FEBS Lett       Date:  1995-01-09       Impact factor: 4.124

6.  Cavities in proteins: structure of a metmyoglobin-xenon complex solved to 1.9 A.

Authors:  R F Tilton; I D Kuntz; G A Petsko
Journal:  Biochemistry       Date:  1984-06-19       Impact factor: 3.162

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Authors:  K W Miller
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8.  Hydrophilicity of cavities in proteins.

Authors:  L Zhang; J Hermans
Journal:  Proteins       Date:  1996-04

9.  Stabilization of the hydrophilic sphere of iobitridol, an iodinated contrast agent, as revealed by experimental and computational investigations.

Authors:  D Meyer; M H Fouchet; M Petta; P A Carrupt; P Gaillard; B Testa
Journal:  Pharm Res       Date:  1995-11       Impact factor: 4.200

10.  The catalytic site of serine proteinases as a specific binding cavity for xenon.

Authors:  M Schiltz; R Fourme; I Broutin; T Prangé
Journal:  Structure       Date:  1995-03-15       Impact factor: 5.006

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  1 in total

Review 1.  Iobitridol: a review of its use as a contrast medium in diagnostic imaging.

Authors:  Paul L McCormack
Journal:  Clin Drug Investig       Date:  2013-02       Impact factor: 2.859

  1 in total

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