Protein design and folding: template trapping of self‐assembled helical bundles

Grell, Daniel; Richardson, Jane S.; Mutter, Manfred

doi:10.1002/psc.308

Cited by 15 publications

(6 citation statements)

References 28 publications

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“…Protein de novo design offers a test of our understanding of the factors controlling protein structure, folding and stability. The approach also offers the prospect of access to tailor-made proteins 9 10 11 12 13 14 15 16 17 . One way to overcome the complexity of protein folding is the concept of template-assembled synthetic proteins (TASPs) 18 19 .…”

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confidence: 99%

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

et al. 2016

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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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confidence: 99%

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

et al. 2016

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“…We describe a β-peptide that forms an amphiphilic helix (lipophilic on one side, hydrophilic on the other), and we show that this molecule undergoes self-association in aqueous solution. Pioneering work from DeGrado, Mutter and others has shown that identifying conventional peptides (α-amino acid residues) that form amphiphilic α-helices and self-associate in small clusters constitutes the initial phase in a “hierarchic” design strategy for helix bundle tertiary structure. , Self-associating α-helices have also formed the basis for self- replicating systems , and provided a platform for exploring unusual sources of noncovalent affinity. , Amphiphilic β-peptide helices have found biological applications, 2a-c but controlled self-association has not previously been observed…”

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confidence: 99%

Toward β-Peptide Tertiary Structure: Self-Association of an Amphiphilic 14-Helix in Aqueous Solution

et al. 2001

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A major frontier in foldamer research is creation of unnatural oligomers that adopt discrete tertiary structures; at present, only biopolymers are known to fold into such compact conformations. We report an initial step toward helix-bundle tertiary structure in the beta-peptide realm by showing that a 10-residue beta-peptide designed to adopt an amphiphilic helical conformation forms small soluble aggregates in water. Sedimentation equilibrium data indicate that the aggregated state falls in the tetramer-hexamer size range. [structure: see text]

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“…shows the synthetic strategy for the preparation of a fourhelix bundle template-assembled synthetic protein [172][173][174][175]. On the other hand the dual character of the Npys group as an S-protecting and S-activating group [147] has permitted the linkage through disulfide bond between artificial carriers and peptide epitopes [170,176].…”

Section: Chemoselective Ligationmentioning

confidence: 99%

Synthetic Approaches for Total Chemical Synthesis of Proteins and Protein-Like Macromolecules of Branched Architecture

Papas¹,

Strongylis²,

Tsikaris

2006

COC

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The progress achieved both in the solid and liquid phase of the synthetic methodologies for peptides, permitted the application of various chemistries for preparing totally synthetic proteins and protein-like macromolecules of branched architecture. Polypeptides with molecular masses in the 10-25 kDa range have been successfully prepared using either the step by step and fragment condensation or the chemoselective ligation methods. Amide, thioether, disulfide, thioester, hydrazone, oxime and thiazolidine linkages have been employed in such syntheses. Fully active proteins or macromolecules mimicking particular protein properties especially in immunology have been synthesized in high purity and large quantities. The branched constructs have found numerous applications in immunology due to their contribution in overcoming the very low ability of short linear peptides to react specifically with antibodies or to induce an immune response. The advantages over almost all the other methods of using synthetic carriers for developing potent antigens and immunogens have placed this approach at the center of extensive research activities. This review focuses on the concept and synthetic strategies suitable for assembling proteins or protein-like macromolecules of branched architecture with application in protein function studies and immunology.

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Protein design and folding: template trapping of self‐assembled helical bundles

Cited by 15 publications

References 28 publications

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

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

Toward β-Peptide Tertiary Structure: Self-Association of an Amphiphilic 14-Helix in Aqueous Solution

Synthetic Approaches for Total Chemical Synthesis of Proteins and Protein-Like Macromolecules of Branched Architecture

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