Department of Chemistry, California Institute for Quantitative Biosciences, Lawrence Berkeley National Laboratory, University of California, Berkeley, California 94720-3220, United States.
Inorg Chem. 2013 Mar 4;52(5):2277-9. doi: 10.1021/ic302685h. Epub 2013 Feb 8.
Heme proteins are exquisitely tuned to carry out diverse biological functions while employing identical heme cofactors. Although heme protein properties are often altered through modification of the protein scaffold, protein function can be greatly expanded and diversified through replacement of the native heme with an unnatural porphyrin of interest. Thus, porphyrin substitution in proteins affords new opportunities to rationally tailor heme protein chemical properties for new biological applications. Here, a highly thermally stable Heme Nitric oxide/OXygen binding (H-NOX) protein is evaluated as a magnetic resonance imaging (MRI) contrast agent. T1 and T2 relaxivities measured for the H-NOX protein containing its native heme are compared to the protein substituted with unnatural manganese(II/III) and gadolinium(III) porphyrins. H-NOX proteins are found to provide unique porphyrin coordination environments and have enhanced relaxivities compared to commercial small-molecule agents. Porphyrin substitution is a promising strategy to encapsulate MRI-active metals in heme protein scaffolds for future imaging applications.
血红素蛋白在采用相同血红素辅基的情况下，能够执行多种不同的生物学功能，其结构设计精妙。虽然血红素蛋白的性质通常通过修饰蛋白支架来改变，但通过将天然血红素替换为感兴趣的非天然卟啉，可以极大地扩展和多样化蛋白功能。因此，在蛋白质中卟啉取代为合理定制血红素蛋白的化学性质以满足新的生物学应用提供了新的机会。在这里，评估了一种高度热稳定的血红素一氧化氮/氧结合（H-NOX）蛋白作为磁共振成像（MRI）造影剂。测量了含有天然血红素的 H-NOX 蛋白的 T1 和 T2 弛豫率，并将其与用非天然锰（II/III）和钆（III）卟啉取代的蛋白进行了比较。与商业小分子试剂相比，H-NOX 蛋白具有独特的卟啉配位环境和增强的弛豫率。卟啉取代是将 MRI 活性金属封装在血红素蛋白支架中用于未来成像应用的一种很有前途的策略。
