Peptide-oligonucleotide conjugates as nanoscale building blocks for assembly of an artificial three-helix protein mimic

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  • Chenguang Lou, University of Southern Denmark
  • ,
  • Manuel C. Martos-Maldonado, University of Copenhagen
  • ,
  • Charlotte Stahl Madsen, University of Copenhagen
  • ,
  • Rasmus P. Thomsen, Biomolecular Nanoscale Engineering Center and Interdisciplinary Nanoscience Center (INANO)
  • ,
  • Søren Roi Midtgaard, University of Copenhagen
  • ,
  • Niels Johan Christensen, University of Copenhagen
  • ,
  • Jørgen Kjems
  • Peter W. Thulstrup, University of Copenhagen
  • ,
  • Jesper Wengel, University of Southern Denmark
  • ,
  • Knud J. Jensen, University of Copenhagen

Peptide-based structures can be designed to yield artificial proteins with specific folding patterns and functions. Template-based assembly of peptide units is one design option, but the use of two orthogonal self-Assembly principles, oligonucleotide triple helix and a coiled coil protein domain formation have never been realized for de novo protein design. Here, we show the applicability of peptide-oligonucleotide conjugates for self-Assembly of higher-ordered protein-like structures. The resulting nano-Assemblies were characterized by ultraviolet-melting, gel electrophoresis, circular dichroism (CD) spectroscopy, small-Angle X-ray scattering and transmission electron microscopy. These studies revealed the formation of the desired triple helix and coiled coil domains at low concentrations, while a dimer of trimers was dominating at high concentration. CD spectroscopy showed an extraordinarily high degree of α-helicity for the peptide moieties in the assemblies. The results validate the use of orthogonal self-Assembly principles as a paradigm for de novo protein design.

Original languageEnglish
Article number12294
JournalNature Communications
Publication statusPublished - 28 Jul 2016

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