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

Chenguang Lou; Manuel Cristo Martos Maldonado; Charlotte Stahl Madsen; Rasmus Peter Thomsen; Søren Roi Midtgaard; Niels Johan Christensen; Jørgen Kjems; Peter Waaben Thulstrup; Jesper Wengel; Knud Jørgen Jensen

doi:10.1038/ncomms12294

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

Chenguang Lou, Manuel Cristo Martos Maldonado, Charlotte Stahl Madsen, Rasmus Peter Thomsen, Søren Roi Midtgaard, Niels Johan Christensen, Jørgen Kjems, Peter Waaben Thulstrup, Jesper Wengel, Knud Jørgen Jensen

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Abstract

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 language	English
Article number	12294
Journal	Nature Communications
Volume	7
Number of pages	9
ISSN	2041-1723
DOIs	https://doi.org/10.1038/ncomms12294
Publication status	Published - 28 Jul 2016

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title = "Peptide–oligonucleotide conjugates as nanoscale building blocks for assembly of an artificial three-helix protein mimic",

abstract = "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.",

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AU - Lou, Chenguang

AU - Martos Maldonado, Manuel Cristo

AU - Madsen, Charlotte Stahl

AU - Thomsen, Rasmus Peter

AU - Midtgaard, Søren Roi

AU - Christensen, Niels Johan

AU - Kjems, Jørgen

AU - Thulstrup, Peter Waaben

AU - Wengel, Jesper

AU - Jensen, Knud Jørgen

PY - 2016/7/28

Y1 - 2016/7/28

N2 - 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.

AB - 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.

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DO - 10.1038/ncomms12294

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VL - 7

JO - Nature Communications

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M1 - 12294

ER -

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

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