Hooker Jacob M, Datta Ankona, Botta Mauro, Raymond Kenneth N, Francis Matthew B
Department of Chemistry, University of California, Berkeley, California 94720-1460, USA.
Nano Lett. 2007 Aug;7(8):2207-10. doi: 10.1021/nl070512c. Epub 2007 Jul 14.
Two high-relaxivity nanoscale magnetic resonance contrast agents have been built using bacteriophage MS2 as a biomolecular scaffold. Protein capsid shells were functionalized on either the exterior or interior surface to display multiple copies of an aldehyde functional group. Subsequently, approximately 90 heteropodal bis(hydroxypyridonate)terephthalamide ligands were attached to these sites through oxime condensation reactions. Upon complexation with Gd3+, contrast agents with ionic relaxivities of up to 41.6 mM-1 s-1 (30 MHz, 25 degrees C) and total molecular relaxivities of up to 3900 mM-1 s-1 (30 MHz, 25 degrees C) were produced. Capsids sequestering the Gd-chelates on the interior surface (attached through tyrosine residues) not only provided higher relaxivities than their exterior functionalized counterparts (which relied on lysine modification) but also exhibited improved water solubility and capsid stability. The attachment functional cargo to the interior surface is envisioned to minimize its influences on biodistribution, yielding significant advantages for tissue targeting by additional groups attached to the capsid exterior.
已利用噬菌体MS2作为生物分子支架构建了两种高弛豫率的纳米级磁共振造影剂。蛋白质衣壳壳层在其外表面或内表面进行功能化，以展示多个醛官能团拷贝。随后，通过肟缩合反应将约90个异足双（羟基吡啶酮）对苯二甲酰胺配体连接到这些位点。与Gd3+络合后，产生了离子弛豫率高达41.6 mM-1 s-1（30 MHz，25℃）和总分弛豫率高达3900 mM-1 s-1（30 MHz，25℃）的造影剂。在内表面螯合Gd螯合物的衣壳（通过酪氨酸残基连接）不仅比其外表面功能化的对应物（依赖赖氨酸修饰）具有更高的弛豫率，而且还表现出改善的水溶性和衣壳稳定性。设想将功能性货物附着在内表面，以尽量减少其对生物分布的影响，通过附着在衣壳外部的其他基团实现组织靶向具有显著优势。
