Design of the elusive proteinaceous oxygen donor copper site suggests a promising future for copper for MRI contrast agents.
Design of the elusive proteinaceous oxygen donor copper site suggests a promising future for copper for MRI contrast agents.
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DOI：
10.1073/pnas.2219036120
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发表时间：
2023-07-04
影响因子：
11.1
通讯作者：
Peacock, Anna F. A.
中科院分区：
文献类型：
--
作者：
Shah, Anokhi;Taylor, Michael J.;Molinaro, Giulia;Anbu, Sellamuthu;Verdu, Margaux;Jennings, Lucy;Mikulska, Iuliia;Diaz-Moreno, Sofia;EL Mkami, Hassane;Smith, Graham M.;Britton, Melanie M.;Lovett, Janet E.;Peacock, Anna F. A.
金属离子在生物学中扮演着许多重要的角色，铜是一种自然选择广泛使用的金属。使用微型人造蛋白质设计策略，已经有可能准备一个新的生物铜结合部位，我们惊讶地发现自然界中没有这种结合部位。由此产生的铜位已被证明具有用于核磁共振造影剂的真正潜力，从而挑战了现有的铜不适合用于核磁共振的教条。这个例子表明，设计非生物金属离子位点是一种强大的方法，可以获得新的工具或试剂，用于生物学以外的应用。我们报道了一种高度难以捉摸的铜位的制备和光谱表征，该铜位仅与蛋白质支架内的氧供体原子结合。尽管铜通常被认为不适合用于MRI造影剂(临床上主要是Gd(III)基)，但设计的铜线圈在临床场强下显示出与Gd(III)类似物相同或更好的弛豫值。这种新的生物蛋白CuOx结合位点的创建展示了从头开始的多肽设计方法在非生物应用中获取化学的能力，例如用于开发MRI造影剂。
Metal ions perform many essential roles in biology, with copper being a metal that nature has chosen to use extensively. Using a miniature artificial protein design strategy, it has been possible to prepare a new-to-biology copper–binding site, one which we were surprised to find is absent in nature. The resulting copper site has been shown to display real potential for use in MRI contrast agents, thereby challenging the existing dogma that copper is unsuitable for use in MRI. This example showcases that designing abiological metal ion sites is a powerful approach for accessing new tools or agents for applications beyond the repertoire of biology. We report the preparation and spectroscopic characterization of a highly elusive copper site bound exclusively to oxygen donor atoms within a protein scaffold. Despite copper generally being considered unsuitable for use in MRI contrast agents, which in the clinic are largely Gd(III) based, the designed copper coiled coil displays relaxivity values equal to, or superior than, those of the Gd(III) analog at clinical field strengths. The creation of this new-to-biology proteinaceous CuOx-binding site demonstrates the power of the de novo peptide design approach to access chemistry for abiological applications, such as for the development of MRI contrast agents.
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DOI：
10.1039/b818306f
发表时间：
2009-04-07
期刊：
Dalton transactions (Cambridge, England : 2003)
影响因子：
--
作者：
Peacock AF;Iranzo O;Pecoraro VL
通讯作者：
Pecoraro VL
影响因子：
15
作者：
Berwick MR;Lewis DJ;Jones AW;Parslow RA;Dafforn TR;Cooper HJ;Wilkie J;Pikramenou Z;Britton MM;Peacock AF
通讯作者：
Peacock AF
影响因子：
3.5
作者：
Dunbar, Lynsey;Sowden, Rebecca J.;Spickett, Corinne M.
通讯作者：
Spickett, Corinne M.
影响因子：
4.5
作者：
Hoogstraten, CG;Britt, RD
通讯作者：
Britt, RD
影响因子：
4.4
作者：
Andreini, Claudia;Banci, Lucia;Rosato, Antonio
通讯作者：
Rosato, Antonio