Design of the elusive proteinaceous oxygen donor copper site suggests a promising future for copper for MRI contrast agents
Date
04/07/2023Author
Grant ID
099149/Z/12/Z
BB/T017740/1
BB/R013780/1
UF090121
Keywords
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Show full item recordAbstract
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 CuO -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.
Citation
Shah , A , Taylor , M J , Molinaro , G , Anbu , S , Verdu , M , Jennings , L , Mikulska , I , Diaz-Moreno , S , El Mkami , H , Smith , G M , Britton , M M , Lovett , J E & Peacock , A F A 2023 , ' Design of the elusive proteinaceous oxygen donor copper site suggests a promising future for copper for MRI contrast agents ' , Proceedings of the National Academy of Sciences of the United States of America , vol. 120 , no. 27 , e2219036120 . https://doi.org/10.1073/pnas.2219036120
Publication
Proceedings of the National Academy of Sciences of the United States of America
Status
Peer reviewed
ISSN
0027-8424Type
Journal article
Description
We thank the Centre for Chemical and Materials Analysis in the School of Chemistry for support of this research. We thank Diamond Light Source for access to beamline I20-Scanning (proposal number SP18941), Horizon 2020 for a Marie Skłodowska-Curie Individual Fellowship (H2020-MSCA-IF-2014-658843) for S.A., EPSRC for funding (EP/K039245/1, EP/R511651/1). We thank the Wellcome Trust for multiuser equipment grant (099149/Z/12/Z) for the high-power Q-band EPR spectrometer and BBSRC (BB/T017740/1) including for the cryogen-free cooling upgrade to the existing X-band (BB/R013780/1). J.E.L. thanks the Royal Society for a University Research Fellowship. M.J.T. and A.S. thank EPSRC for doctoral funding (EP/M508214/1) and (EP/L015110/1), respectively.Collections
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