Inorganic Chemistry

Dynamic Stereoselection of Peptide Helicates and Their Selective Labeling of DNA Replication Foci in Cells


Peptide engineering has been extremely successful in creating new structures with defined properties and functions. Although generally overlooked in this context, coordination chemistry offers an additional set of interactions that opens unexplored design opportunities for developing complex molecular structures. With this in mind, we report the development of new artificial peptide ligands that fold into chiral and discrete supramolecular helicates in the presence of labile metal ions such as Fe(II) and Co(II). By selecting appropriate heterochiral β‑turn promoting sequences, we can encode the stereoselective folding of the peptide ligand, and define the physicochemical properties of their corresponding metal complexes. The study of these metallopeptides by CD and NMR spectroscopy, combined with computational methods allowed us to identify and determine the structure of two isochiral ΛΛ-helicates, folded as topological isomers. We also show that these new peptide helicates, dynamically selected in the presence of labile Co(II) ions, can be locked as kinetically-inert species by in situ oxidation to Co(III). Finally, in addition to the in vitro characterization of their selective binding to three-way DNA, cell microscopy experiments demonstrated that a rhodamine-labeled Fe(II) helicate was internalized and selectively stains DNA replication factories in functional cells.

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Manuscript submitted for publication.


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Supplementary material

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Supporting Information