Abstract
Naturally occurring peptides in many living systems perform antimicrobial and anticancer host defence roles, but their potential for clinical application is limited by low metabolic stability and relatively high costs of goods. Self-assembled helical metal complexes provide an attractive synthetic platform for non-peptidic architectures that can emulate some of the properties of short cationic α-helical peptides, with tuneable charge, shape, size and amphipathicity. Correspondingly there is a growing body of evidence demonstrating that these supramolecular architectures exhibit bioactivity that emulates that of the natural systems. We review that evidence in the context of synthetic advances in the area, driven by the potential for biomedical applications. We note some design considerations for new biologically-relevant metallohelices, and give our outlook on the future of these compounds as therapeutic peptidomimetics.
Highlights
In coordination complexes, the metal ions can be considered to be structural loci, providing anchoring points for the spatial distribution of coordinated ligand scaffolds, as controlled by electronic preference for particular geometries or via steric and secondary interactions
He undertook his PhD with Professor Peter Scott at the University of Warwick, developing highly functionalised peptidomimetic metallohelices
Apparent binding constants have been measured for several compounds via ethidium bromide displacement, including P-2 [Fe(II) analogue],52 racemic-3-Co(III),[53] meso-6,22 D-9a,36‡ D-10,36 D-12,47 D-13,38 D15;47 the measured Kapp lie in the range 106 to 108, we note the strong dependency on ionic strength
Summary
He undertook his PhD with Professor Peter Scott at the University of Warwick, developing highly functionalised peptidomimetic metallohelices. A er completing a polymer focused research project under the supervision of Professor Peter Scott in the nal year of his degree, he continued to pursue his doctoral research within the Scott research group and is currently in the third year of his PhD His current research focuses on design, development and biological studies of functionalised optically pure metallohelices, with a particular emphasis on their antimicrobial behaviours and mechanisms of action. This begs the question – can we emulate the biological functions of peptide ahelices using metallohelices, for applications in biomedicine?
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