TY - JOUR
T1 - A de novo designed monomeric, compact three helix bundle protein on a carbohydrate template
AU - Malik, Leila
AU - Nygård, Jesper
AU - Christensen, Niels Johan
AU - Madsen, Charlotte Stahl
AU - Rösner, Heike Ilona
AU - Kragelund, Birthe Brandt
AU - Høiberg-Nielsen, Rasmus
AU - Streicher, Werner
AU - Arleth, Lise
AU - Thulstrup, Peter Waaben
AU - Jensen, Knud Jørgen
N1 - © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
PY - 2015/9/1
Y1 - 2015/9/1
N2 - De novo design and chemical synthesis of proteins and of other artificial structures that mimic them is a central strategy for understanding protein folding and for accessing proteins with new functions. We have previously described carbohydrates that act as templates for the assembly of artificial proteins, so-called carboproteins. The hypothesis is that the template preorganizes the secondary structure elements and directs the formation of a tertiary structure, thus achieving structural economy in the combination of peptide, linker, and template. We speculate that the structural information from the template could facilitate protein folding. Here we report the design and synthesis of three-helix-bundle carboproteins on deoxyhexopyranosides. The carboproteins were analyzed by CD, analytical ultracentrifugation (AUC), small-angle X-ray scattering (SAXS), and NMR spectroscopy, and this revealed the formation of the first compact and folded monomeric carboprotein, distinctly different from a molten globule. En route to this carboprotein we observed a clear effect originating from the template on protein folding.
AB - De novo design and chemical synthesis of proteins and of other artificial structures that mimic them is a central strategy for understanding protein folding and for accessing proteins with new functions. We have previously described carbohydrates that act as templates for the assembly of artificial proteins, so-called carboproteins. The hypothesis is that the template preorganizes the secondary structure elements and directs the formation of a tertiary structure, thus achieving structural economy in the combination of peptide, linker, and template. We speculate that the structural information from the template could facilitate protein folding. Here we report the design and synthesis of three-helix-bundle carboproteins on deoxyhexopyranosides. The carboproteins were analyzed by CD, analytical ultracentrifugation (AUC), small-angle X-ray scattering (SAXS), and NMR spectroscopy, and this revealed the formation of the first compact and folded monomeric carboprotein, distinctly different from a molten globule. En route to this carboprotein we observed a clear effect originating from the template on protein folding.
U2 - 10.1002/cbic.201500285
DO - 10.1002/cbic.201500285
M3 - Journal article
C2 - 26147795
SN - 1439-4227
VL - 16
SP - 1905
EP - 1918
JO - ChemBioChem
JF - ChemBioChem
IS - 13
ER -