Metallo-coiled Coil Stabilization via Chemical Cross-Linking: Implications for Gd(III)-Based MRI Contrast Agents
Coiled coils are a versatile class of protein-inspired metal-binding ligands with well-defined sequence-to-structure relationships and high synthetic accessibility, making them promising tunable ligands for applications spanning biomedical imaging, catalysis, and material science. However, their practical utility is often limited by poor stability, particularly under physiological conditions. Herein, we introduce a covalent interhelical isopeptide cross-linking strategy that significantly enhances the thermal, thermodynamic, kinetic, and proteolytic stability of lanthanide-bound coiled coils designed for use as MRI contrast agents. Biophysical analysis, including CD, native MS, HPLC, and fluorescence assays, reveal that introduction of a single cross-linking layer promotes structural organization, driving the peptide from an unfolded to a well-folded state. Cross-linking leads to a remarkable 2.5 Γ 108-fold enhancement in metal-binding affinity, along with greater kinetic stability and resistance to proteolytic degradation compared to the non-cross-linked analogue. 1H relaxometric studies and molecular dynamics simulations reveal that this class of potential MRI contrast agents operates via a second-sphere water coordination mechanism. Optimized cross-linking improves MRI efficacy by βΌ30% at clinically relevant field strengths, highlighting its potential as a design principle for next-generation MRI contrast agents. Beyond MRI, these findings underscore the broader potential of covalent cross-linking strategies for enhancing the stability and functionality of metallo-coiled coils, expanding their utility across diverse applications.
Exciting news from our group β our latest paper has just been published in JACS! π
Congratulations to @ka-hadley.bsky.social on her first publication, and sincere thanks to all our collaborators for their amazing contributions.
π pubs.acs.org/doi/10.1021/...
06.11.2025 15:11 β π 7 π 1 π¬ 0 π 0
Design of MRI contrast agents based on designed metallo coiled coils at University of Birmingham on FindAPhD.com
PhD Project - Design of MRI contrast agents based on designed metallo coiled coils at University of Birmingham, listed on FindAPhD.com
π¬ Weβre recruiting 2 PhD students (one funded via BBSRC/MIBTP, deadline Nov 27) to work on MRI contrast agents based on de novo metallo-coiled coils.
Interested or know someone who might be? Please share or get in touch! π
π findaphd.com/p189432
28.10.2025 08:52 β π 1 π 0 π¬ 0 π 0
Truly honoured to receive this award from the RSC CBBG Interest Group! Grateful to my mentors, collaborators, and especially the lab team (past and present) - couldnβt have done it without you.
22.10.2025 06:45 β π 3 π 0 π¬ 0 π 0
Weβre looking for talented postdocs! Join our group in Birmingham in the brand-new Molecular Sciences Building @uobchemistry.bsky.social π§ͺ Apply for a Marie SkΕodowska-Curie Fellowship to work with us on cutting-edge metallopeptide design.
Get in touch to discuss ideas! #MSCA #postdoc #chemistry
29.04.2025 14:16 β π 2 π 1 π¬ 0 π 0
Was a real pleasure to visit the inspiring CiQUS! Great science, great colleagues and a great environment!
29.04.2025 13:51 β π 3 π 0 π¬ 0 π 0
Thanks to Rebeca GarcΓa, Anna Peacock @peacockgroup.bsky.social and Antonio Caballero for helping Jose in his day. Congrats Jose Great Job!
10.04.2025 21:07 β π 5 π 1 π¬ 0 π 0
Less than 2 weeks left to register for #Dalton2025. All the info on the webpage: www.rsc.org/events/detai... We look forward to seeing you there!
25.02.2025 13:53 β π 2 π 1 π¬ 0 π 0
A painting of a clocktower drawn from different coloured molecules.
A close up of the clocktower drawing reveals the molecules that make up the artwork.
We have unveiled this amazing picture of the iconic Old Joe clocktower by School alumnus Lucy Walker, drawn using molecules, in the foyer of our new home the Molecular Sciences Building #chemsky
17.02.2025 09:25 β π 24 π 8 π¬ 2 π 2
10 days left to submit your abstract for an oral presentation at #Dalton2025. All the info on the webpage: www.rsc.org/events/detai... We look forward to seeing you there!
30.01.2025 12:37 β π 1 π 1 π¬ 0 π 0
Dalton 2025
Save The Date!
#Dalton2025 conference will be held at the University of Warwick on April 1-3, 2025
Registration will be online soon π
www.rsc.org/events/detai...
16.12.2024 13:51 β π 4 π 3 π¬ 0 π 1
Two more days till the deadline - Please reach out if you have any questions or want to know more. Thanks
10.12.2024 14:45 β π 1 π 3 π¬ 0 π 0
One more week till the deadline - Please reach out if you have any questions or want to know more. Thanks
05.12.2024 11:18 β π 1 π 3 π¬ 0 π 0
Research Fellow at University of Birmingham
Looking for a new job opportunity in academia? Check out this job opening for a Research Fellow on jobs.ac.uk!
We're recruiting two PDRAs (one computational and one experimental) to join the project "Designer metallo coiled coils for use in MRI" - closing date Dec.12th. Please get in touch if you'd like to know more. @uobchemistry.bsky.social
www.jobs.ac.uk/job/DKS611/r...
www.jobs.ac.uk/job/DKS605/r...
21.11.2024 10:16 β π 2 π 5 π¬ 0 π 2
Royal Society of Chemistry Interest Group for Chemical Biology and Bioorganic Chemistry
Engineering artificial metalloenzymes and photoenzymes at TU Munich
https://www.bio.nat.tum.de/en/proteinchemie
Royal Society Dorothy Hodgkin Fellow at School of Chemistry, University of Birmingham. Supramolecular chemistry and polymer nanotechnology. https://www.fieldengroup.net/
Assistant Professor at the University of Nottingham.
A Royal Society of Chemistry, Dalton Council Interest Group. The IBDG serves the UK community of Inorganic Biochemists and Bioinorganic Chemists.
ibdgorguk.wordpress.com
Research Chemist, https://researchportal.bath.ac.uk/en/persons/sofia-pascu/
Professor of Bioinorganic and Materials Chemistry, FRSC, FHEA, @uniofbath.bsky.social #StCatzOxford β97 #Balliol β98 #LMHOxford Beaufort Visiting Fellowβ23 #research #ERC #O2Sense
Coordinating synthetic and engineering biology research and innovation across Bristol. Official account of the University of Bristol.
https://www.bristol.ac.uk/biodesign-institute
Bioinorganic research with medicinal and catalytic applications under the supervision of Prof. Anne-Kathrin Duhme-Klair | University of York @uniofyork.bsky.social
Assistant Prof. University of Birmingham School of Chemistry. Systems Chemistry, Physical Organic Chemistry and Soft Matter
https://www.maguire-research-group.com/
#UKRIFLF and Group Leader in the Physical Sciences, Francis Crick Institute, Senior Lecturer, KCL. Supramolecular Chemist; Molecular Machines and Capsules; Supramolecular Therapeutics; Peptide Chemistry and Chemical Biology
CatedrΓ‘tica QuΓmica InorgΓ‘nica UAM. Spain. Metals in Medicine. Medicinal Chemistry.
With the future of the world in the balance, everyone has a role to play in making it better. How will you join in?
π Website: www.rsc.org
Welcome to the Bluesky account of the School of Chemistry at the University of Birmingham.
Chemistry passionist combining bioinorganic chemistry with sustainable polymerisation catalysis and chemical data management for ML at RWTH Aachen University, Germany
https://www.bioac.ac.rwth-aachen.de/
Husband, Dad, PhD, pedant, former Chief Ed of @natchem.nature.com, now Editorial Director at @NaturePortfolio.nature.com. Wine, chemistry, publishing, words & snark. Views ranty, but all mine. #ContaminatedBlood victim (affected). He/Him
Chemistry outreach project based at the University of Birmingham. We are passionate about making chemistry fun and accessible for everyone. www.chembam.com
Chemistry Professor, University of Rochester, USA. Proud PI of @BrenLab.bsky.social
Bioinorganic Chemistry | Postdoc @daumannl.bsky.social @HHU.de | she/her | Lanthanides are awesome!π€ | science communication π«Ά | @munichsoapbox.bsky.social
