Selective lanthanide binding sites engineered within a De Novo designed coiled coil

Slope, Louise Nicola (2018). Selective lanthanide binding sites engineered within a De Novo designed coiled coil. University of Birmingham. Ph.D.

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De novo designed coiled coils are described that are capable of selectively discriminating between Ln3+ ions. Sites buried within the hydrophobic core are able to actively discriminate against both larger and smaller ions. Whereas linearly translating the binding site towards the N-terminus, ‘turns-off’ selectivity, owing to N-terminal fraying and flexibility. Mutating first sphere coordinating and second sphere non-coordinating residues was found to impact on the metal coordination chemistry, including the hydration state of the bound Tb3+, which in turn led to altered metal selectivity and MRI relaxivities of the Gd3+ complexes. Given these findings, a novel two binding site coiled coil trimer was designed in which incorporation of both a ‘buried’ and N-terminal site enabled two different Ln3+ ions with differing properties to be bound within a single system. This dual lanthanide binding construct resembles a significant development within the field, being the first example established in a peptide assembly, and is notably even capable of selectively binding and discriminating between two different, but similar, Ln3+ ions. Translating the second Ln3+ binding site linearly along the coiled coil resulted in a series of dual Ln3+ binding peptides in which the distance between the metal ions can be controlled.

Type of Work: Thesis (Doctorates > Ph.D.)
Award Type: Doctorates > Ph.D.
College/Faculty: Colleges (2008 onwards) > College of Engineering & Physical Sciences
School or Department: School of Chemistry
Funders: Engineering and Physical Sciences Research Council, Other
Other Funders: The University of Birmingham
Subjects: Q Science > QD Chemistry


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