Coiled coils as ligands for inclusion in the inorganic chemist's toolbox

Proteins are versatile and powerful ligands for metal ions, capable of facilitating unusual coordination chemistries and imparting unique chemical properties. These features are often challenging to replicate using small-molecule ligands, sparking significant interest in developing robust, self-assembling protein scaffolds as novel ligands for applications in inorganic chemistry. This raises the question: can artificial metal-protein complexes be designed to perform functions beyond those found in nature?

In this context, our research has focused on the development of candidate MRI contrast agents based on paramagnetic metal ions coordinated by such a class of ligands. Our ligands are peptide coiled coils, or supercoiled helices, with a hydrophobic core that can be tailored to create a metal-binding site optimised for coordination chemistry. We have demonstrated that the efficiency of gadolinium(III), a metal widely used in MRI contrast agents, is significantly enhanced when complexed with our designed coiled-coil scaffold. Moreover, the performance of these complexes can be predictably tuned through de novo peptide design.

Recently, we extended this approach to copper(II), showing that coiled-coil coordination can endow it with MRI contrast properties – something that was previously thought impossible. This strategy not only makes copper(II) suitable for potential use in MRI contrast agent design, but also results in a more efficient performance compared to some current clinical agents.

Host: Charlotte Willans (charlotte.willans@york.ac.uk).