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

Although largely overlooked in peptide engineering, coordination chemistry offers a new set of interactions that opens unexplored design opportunities for developing complex molecular structures. In this context, we report new artificial peptide ligands that fold into chiral helicates in the presenc...

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Bibliographic Details
Published in:Angewandte Chemie 2021-04, Vol.133 (16), p.8941-8948
Main Authors: Gómez‐González, Jacobo, Pérez, Yolanda, Sciortino, Giuseppe, Roldan‐Martín, Lorena, Martínez‐Costas, José, Maréchal, Jean‐Didier, Alfonso, Ignacio, Vázquez López, Miguel, Vázquez, M. Eugenio
Format: Article
Language:English
Subjects:
Chemistry
Circular dichroism
Computer applications
coordination chemistry
Coordination compounds
Deoxyribonucleic acid
Dichroism
DNA
DNA biosynthesis
DNA recognition
Industrial engineering
Isomers
Ligands
Magnetic resonance spectroscopy
Manufacturing engineering
Metal complexes
Metal ions
metallopeptides
Molecular structure
NMR
NMR spectroscopy
Nuclear magnetic resonance
peptide design
Peptides
Physicochemical properties
Replication
Rhodamine
Selective binding
Stereoselectivity
supramolecular chemistry
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Summary:Although largely overlooked in peptide engineering, coordination chemistry offers a new set of interactions that opens unexplored design opportunities for developing complex molecular structures. In this context, we report new artificial peptide ligands that fold into chiral helicates in the presence of labile metal ions such as FeII and CoII. Heterochiral β‐turn‐promoting sequences encode the stereoselective folding of the peptide ligands and define the physicochemical properties of their corresponding metal complexes. Circular dichroism and NMR spectroscopy in combination with computational methods allowed us to identify and determine the structure of two isochiral ΛΛ‐helicates, folded as topological isomers. Finally, in addition to the in‐vitro characterization of their selective binding to DNA three‐way junctions, cell‐microscopy experiments demonstrated that a rhodamine‐labeled FeII helicate was internalized and selectively stains DNA replication factories in functional cells. Artificial bipyridine‐containing peptide ligands encode in their sequence the stereoselective folding into chiral three‐stranded FeII or CoII peptide helicates and as kinetically inert dinuclear CoIII complexes by in‐situ oxidation. These peptide helicates selectively label DNA replication foci in functional cells.
ISSN:0044-8249
1521-3757
DOI:10.1002/ange.202013039