Prangé T, Neuman A, Corot C, Meyer D
Chimie Structurale Biomoleculaire (URA-1430 CNRS, Bobigny, France.
Pharm Res. 1997 Dec;14(12):1713-7. doi: 10.1023/a:1012123628123.
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.
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.
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.
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.
亲水性球体稳定化或疏水屏蔽的概念已在血管成像中生物相容性造影剂的合成中被提出。为提高这些多碘化剂的安全性，应尽可能降低其与生物大分子中蛋白质疏水位点的相互作用。为评估与蛋白质的相互作用水平，我们选择了在碘比醇（泽尼克）存在下的丝氨酸蛋白酶弹性蛋白酶作为模型。
利用0.98埃的同步辐射，通过X射线衍射技术对饱和单晶上的碘比醇与猪胰弹性蛋白酶之间的复合物进行了研究。
与碘海醇不同，碘海醇显示出多种相互作用，包括在活性位点的一种相互作用，而碘比醇无法直接与弹性蛋白酶相互作用。在晶体堆积的两个分子之间仅发现一个部分占据的位点。
碘比醇分子设计起源的“疏水屏蔽”概念的验证已被证明是最小化体内蛋白质相互作用的一个基本特征。
