Chemistry - A European Journal
Chemistry - A European Journal
5 years ago

Folding Topology of a Short Coiled-Coil Peptide Structure Templated by an Oligonucleotide Triplex

Folding Topology of a Short Coiled-Coil Peptide Structure Templated by an Oligonucleotide Triplex
Niels Johan Christensen, Jesper Wengel, Peter W. Thulstrup, Kasper K. Sørensen, Søren Roi Midtgaard, Manuel C. Martos-Maldonado, Knud J. Jensen, Chenguang Lou, Maria Ejlersen
The rational design of a well-defined protein-like tertiary structure formed by small peptide building blocks is still a formidable challenge. By using peptide–oligonucleotide conjugates (POC) as building blocks, we present the self-assembly of miniature coiled-coil α-helical peptides guided by oligonucleotide duplex and triplex formation. POC synthesis was achieved by copper-free alkyne–azide cycloaddition between three oligonucleotides and a 23-mer peptide, which by itself exhibited multiple oligomeric states in solution. The oligonucleotide domain was designed to furnish a stable parallel triplex under physiological pH, and to be capable of templating the three peptide sequences to constitute a small coiled-coil motif displaying remarkable α-helicity. The formed trimeric complex was characterized by ultraviolet thermal denaturation, gel electrophoresis, circular dichroism (CD) spectroscopy, small-angle X-ray scattering (SAXS), and molecular modeling. Stabilizing cooperativity was observed between the trimeric peptide and the oligonucleotide triplex domains, and the overall molecular size (ca. 12 nm) in solution was revealed to be independent of concentration. The topological folding of the peptide moiety differed strongly from those of the individual POC strands and the unconjugated peptide, exclusively adopting the designed triple helical structure. Creating scaffolds: A miniature trimeric coiled-coil motif was assembled by hybridization of an oligonucleotide triple helix template (see figure).

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/chem.201700971

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