Datta Ankona, Hooker Jacob M, Botta Mauro, Francis Matthew B, Aime Silvio, Raymond Kenneth N
Department of Chemistry, University of California, Berkeley, California 94720-1460, USA.
J Am Chem Soc. 2008 Feb 27;130(8):2546-52. doi: 10.1021/ja0765363. Epub 2008 Feb 5.
High relaxivity macromolecular contrast agents based on the conjugation of gadolinium chelates to the interior and exterior surfaces of MS2 viral capsids are assessed. The proton nuclear magnetic relaxation dispersion (NMRD) profiles of the conjugates show up to a 5-fold increase in relaxivity, leading to a peak relaxivity (per Gd3+ ion) of 41.6 mM(-1) s(-1) at 30 MHz for the internally modified capsids. Modification of the exterior was achieved through conjugation to flexible lysines, while internal modification was accomplished by conjugation to relatively rigid tyrosines. Higher relaxivities were obtained for the internally modified capsids, showing that (i) there is facile diffusion of water to the interior of capsids and (ii) the rigidity of the linker attaching the complex to the macromolecule is important for obtaining high relaxivity enhancements. The viral capsid conjugated gadolinium hydroxypyridonate complexes appear to possess two inner-sphere water molecules (q = 2), and the NMRD fittings highlight the differences in the local motion for the internal (tauRl = 440 ps) and external (tauRl = 310 ps) conjugates. These results indicate that there are significant advantages of using the internal surface of the capsids for contrast agent attachment, leaving the exterior surface available for the installation of tissue targeting groups.
对基于钆螯合物与MS2病毒衣壳内外表面共轭的高弛豫率大分子造影剂进行了评估。共轭物的质子核磁共振弛豫分散（NMRD）曲线显示弛豫率提高了5倍，对于内部修饰的衣壳，在30 MHz时的峰值弛豫率（每Gd3+离子）达到41.6 mM(-1) s(-1)。通过与柔性赖氨酸共轭实现外部修饰，而通过与相对刚性的酪氨酸共轭完成内部修饰。内部修饰的衣壳获得了更高的弛豫率，表明（i）水能够轻易扩散到衣壳内部，以及（ii）将复合物连接到大分子的连接子的刚性对于获得高弛豫率增强很重要。病毒衣壳共轭的羟基吡啶钆配合物似乎拥有两个内球水分子（q = 2），NMRD拟合突出了内部（tauRl = 440 ps）和外部（tauRl = 310 ps）共轭物局部运动的差异。这些结果表明，将造影剂连接在衣壳内表面有显著优势，使得外表面可用于安装组织靶向基团。
