title: A de Novo-Designed Monomeric, Compact Three-Helix-Bundle Protein on a Carbohydrate Template.
abstract: 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.
authors.affiliation: Department of Chemistry, Faculty of Science, University of Copenhagen, Thorvaldsensvej 40, 1871 Frederiksberg (Denmark).
authors.forename: Leila
authors.initials: L
authors.lastname: Malik
authors.affiliation: Niels Bohr Institute, Faculty of Science, University of Copenhagen, Blegdamsvej 17, 2100 Copenhagen (Denmark).
authors.forename: Jesper
authors.initials: J
authors.lastname: Nygaard
authors.affiliation: Department of Chemistry, Faculty of Science, University of Copenhagen, Thorvaldsensvej 40, 1871 Frederiksberg (Denmark).
authors.forename: Niels J
authors.initials: NJ
authors.lastname: Cristensen
authors.affiliation: Department of Chemistry, Faculty of Science, University of Copenhagen, Thorvaldsensvej 40, 1871 Frederiksberg (Denmark).
authors.forename: Charlotte S
authors.initials: CS
authors.lastname: Madsen
authors.affiliation: Department of Biology, SBin Laboratory, Faculty of Science, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen (Denmark).
authors.forename: Heike I
authors.initials: HI
authors.lastname: Rösner
authors.affiliation: Department of Biology, SBin Laboratory, Faculty of Science, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen (Denmark).
authors.forename: Birthe B
authors.initials: BB
authors.lastname: Kragelund
authors.affiliation: Niels Bohr Institute, Faculty of Science, University of Copenhagen, Blegdamsvej 17, 2100 Copenhagen (Denmark).
authors.forename: Rasmus
authors.initials: R
authors.lastname: Hoiberg-Nielsen
authors.affiliation: Novozymes A/S, Krogshoejvej 36, 2880 Bagsvaerd (Denmark).
authors.forename: Werner W
authors.initials: WW
authors.lastname: Streicher
authors.affiliation: Niels Bohr Institute, Faculty of Science, University of Copenhagen, Blegdamsvej 17, 2100 Copenhagen (Denmark).
authors.forename: Lise
authors.initials: L
authors.lastname: Arleth
authors.affiliation: Department of Chemistry, Faculty of Science, University of Copenhagen, Thorvaldsensvej 40, 1871 Frederiksberg (Denmark).
authors.forename: Peter W
authors.initials: PW
authors.lastname: Thulstrup
authors.affiliation: Department of Chemistry, Faculty of Science, University of Copenhagen, Thorvaldsensvej 40, 1871 Frederiksberg (Denmark).
authors.forename: Knud J
authors.initials: KJ
authors.lastname: Jensen
keywords: bioorganic chemistry; carbohydrates; oximes; peptides; proteins