Periodic Reporting for period 1 - UCLnProt (De novo design of an UpConverting metalloProtein)
Reporting period: 2019-09-02 to 2021-09-01
This project developed a library of coiled coils, a new class of ligands for lanthanide ions, and generated a series of lanthanide complexes. The traditional field of lanthanide chemistry has focussed primarily on the use of traditional small molecule ligands. This work therefore provides a new class of ligands to the lanthanide coordination chemistry toolbox. Furthermore, lanthanide biochemistry is a field only a decade in the making. Consequently, the coordination of lanthanides to miniature protein scaffolds, our coiled coils, and the interrogation of resulting coordination chemistry, provides useful insight into lanthanide biochemistry.
Uni-, bi- and tri-metallic coiled coils were designed and interrogated. Comparisons between the different designs and the spectroscopic outputs led to the establishment of some key structure-function relationships, which ultimately allowed for the more precise tuneable design of “functional” lanthanide sites.
The results obtained have been communicated to the international scientific academic community in several national and international conferences. In total this results in 8 posters and 1 oral communication over the last two years, in addition to weekly and monthly presentations at regular group meetings. Despite the COVID-19 lockdown and subsequent restrictions, I was also able to deliver several talks on the project to the general public (within the UK). Pleasingly these activities are still ongoing and continue despite the project formally coming to an end.
De novo designed peptides allows one to effectively engineer 3D metal-binding sites within a peptide scaffold with predictable secondary, tertiary and quaternary structure, for metal ion coordination. This offers the synthetic advantages of small molecule complexes, whilst retaining the core elements, and importantly advantages, of natural proteins. De novo designed peptides offer a simplified and robust scaffold with which one can more readily establish important structure–function relationships. As for other metals, the coordination environment plays an essential role in the coordination chemistry and resulting lanthanide complexes physical properties. We developed several designs able to bind two or three lanthanide ions and obtain both homo- and hetero- bimetallic coiled coils. The stability and the photophysicial properties of these scaffolds were evaluated and on the base of these results new improved sequences were redesign and synthetized.