Design of the elusive proteinaceous oxygen donor copper site suggests a promising future for copper for MRI contrast agents

Anokhi Shah; Michael J Taylor; Giulia Molinaro; Sellamuthu Anbu; Margaux Verdu; Lucy Jennings; Iuliia Mikulska; Sofia Diaz-Moreno; Hassane El Mkami; Graham M Smith; Melanie M Britton; Janet E Lovett; Anna F A Peacock

doi:10.1073/pnas.2219036120

Design of the elusive proteinaceous oxygen donor copper site suggests a promising future for copper for MRI contrast agents

Anokhi Shah, Michael J Taylor, Giulia Molinaro, Sellamuthu Anbu, Margaux Verdu, Lucy Jennings, Iuliia Mikulska, Sofia Diaz-Moreno, Hassane El Mkami, Graham M Smith, Melanie M Britton, Janet E Lovett^*, Anna F A Peacock^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Article number	e2219036120
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	120
Issue number	27
Early online date	26 Jun 2023
DOIs	https://doi.org/10.1073/pnas.2219036120
Publication status	Published - 4 Jul 2023

Keywords

coiled coil
Magnetic Resonance Imaging
Binding Sites
bioinorganic chemistry
contrast agents
MRI
Peptides
Contrast Media - chemistry
protein design
Copper - metabolism

Access to Document

10.1073/pnas.2219036120Licence: CC BY

Shah_2023_PNAS_Design-elusive-proteinaceous_CC
Copyright © 2023 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY).
Final published version, 1.17 MBLicence: CC BY

Enabling Shaped Pulse Capability: Enabling Shaped Pulse Capability for Superior Biological Structural Determination Using EPR Spectroscopy.
Lovett, J. E. (PI), Bode, B. E. (CoI), Penedo, C. (CoI), Pitt, S. J. (CoI), Schwarz-Linek, U. (CoI), Smith, G. M. (CoI), Watson, A. J. B. (CoI) & White, M. (CoI)
BBSRC
1/10/20 → 30/09/21
Project: Standard
Cryogen-free arbitrary waveform EPR: Cryogen-free arbitrary waveform EPR for structural Biology and Biophysics
Bode, B. E. (PI), Lovett, J. E. (CoI), Pliotas, C. (CoI), Schwarz-Linek, U. (CoI), Smith, G. M. (CoI), Stewart, A. J. (CoI) & White, M. (CoI)
1/05/18 → 30/04/19
Project: Standard
Royal Society Research Fellowship: Royal Society Research Fellowship
Lovett, J. E. (PI)
The Royal Society
1/05/14 → 15/02/17
Project: Fellowship

Design of the elusive proteinaceous oxygen donor copper site suggests a promising future for copper for MRI contrast agents (dataset)
Shah, A. (Creator), Taylor, M. J. (Creator), El Mkami, H. (Creator), Smith, G. M. (Creator) & Lovett, J. E. (Creator), University of St Andrews, 31 Jul 2023
DOI: 10.17630/835ab42b-5999-4437-8ccb-34cdc630a179
Dataset

File
Data underpinning Michael James Taylor's thesis
Taylor, M. J. (Creator), Lovett, J. E. (Supervisor) & Smith, G. M. (Supervisor), University of St Andrews, 14 May 2026
DOI: 10.17630/48cec54e-ef27-40d6-b5bf-03ca102c85b2, https://doi.org/10.17630/sta/915
Dataset: Thesis dataset

Cite this

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, 120(27), Article e2219036120. https://doi.org/10.1073/pnas.2219036120

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title = "Design of the elusive proteinaceous oxygen donor copper site suggests a promising future for copper for MRI contrast agents",

abstract = "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.",

keywords = "coiled coil, Magnetic Resonance Imaging, Binding Sites, bioinorganic chemistry, contrast agents, MRI, Peptides, Contrast Media - chemistry, protein design, Copper - metabolism",

author = "Anokhi Shah and Taylor, {Michael J} and Giulia Molinaro and Sellamuthu Anbu and Margaux Verdu and Lucy Jennings and Iuliia Mikulska and Sofia Diaz-Moreno and {El Mkami}, Hassane and Smith, {Graham M} and Britton, {Melanie M} and Lovett, {Janet E} and Peacock, {Anna F A}",

note = "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 Sk{\l}odowska-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.",

year = "2023",

month = jul,

day = "4",

doi = "10.1073/pnas.2219036120",

language = "English",

volume = "120",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

issn = "0027-8424",

publisher = "NATL ACAD SCIENCES",

number = "27",

}

Shah, A, Taylor, MJ, Molinaro, G, Anbu, S, Verdu, M, Jennings, L, Mikulska, I, Diaz-Moreno, S, El Mkami, H , Smith, GM, Britton, MM, Lovett, JE & Peacock, AFA 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

Design of the elusive proteinaceous oxygen donor copper site suggests a promising future for copper for MRI contrast agents. / Shah, Anokhi; Taylor, Michael J; Molinaro, Giulia et al.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 120, No. 27, e2219036120, 04.07.2023.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Design of the elusive proteinaceous oxygen donor copper site suggests a promising future for copper for MRI contrast agents

AU - Shah, Anokhi

AU - Taylor, Michael J

AU - Molinaro, Giulia

AU - Anbu, Sellamuthu

AU - Verdu, Margaux

AU - Jennings, Lucy

AU - Mikulska, Iuliia

AU - Diaz-Moreno, Sofia

AU - El Mkami, Hassane

AU - Smith, Graham M

AU - Britton, Melanie M

AU - Lovett, Janet E

AU - Peacock, Anna F A

N1 - 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.

PY - 2023/7/4

Y1 - 2023/7/4

N2 - 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.

AB - 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.

KW - coiled coil

KW - Magnetic Resonance Imaging

KW - Binding Sites

KW - bioinorganic chemistry

KW - contrast agents

KW - MRI

KW - Peptides

KW - Contrast Media - chemistry

KW - protein design

KW - Copper - metabolism

U2 - 10.1073/pnas.2219036120

DO - 10.1073/pnas.2219036120

M3 - Article

C2 - 37364102

SN - 0027-8424

VL - 120

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 27

M1 - e2219036120

ER -

Design of the elusive proteinaceous oxygen donor copper site suggests a promising future for copper for MRI contrast agents

Abstract

Keywords

Access to Document

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Projects

Enabling Shaped Pulse Capability: Enabling Shaped Pulse Capability for Superior Biological Structural Determination Using EPR Spectroscopy.

Cryogen-free arbitrary waveform EPR: Cryogen-free arbitrary waveform EPR for structural Biology and Biophysics

Royal Society Research Fellowship: Royal Society Research Fellowship

Datasets

Design of the elusive proteinaceous oxygen donor copper site suggests a promising future for copper for MRI contrast agents (dataset)

Data underpinning Michael James Taylor's thesis

Cite this