Extending the concept of template-assembled synthetic proteins.
The creation of native-like macromolecules in copying nature's way represents a fascinating challenge in protein chemistry today. In the absence of a detailed knowledge of the complex folding pathway the ultimate goal in protein de novo design, the construction of artificial proteins with predetermined three-dimensional structure and tailor-made functions based on a defined, generally valid set of rules, appears to be still out of reach. With progress in synthesis strategies and biostructural characterization methods, topological templates have become a versatile tool for inducing and stabilizing secondary and tertiary structures, such as protein loops, beta-turns, alpha-helices, beta-sheets and a variety of folding motifs. In this article, we extend the concept of template-assembled synthetic proteins for the construction of protein-like topologies with multiply bridged, oligocyclic chain architectures termed locked-in tertiary folds that exhibit unique physicochemical and folding properties because of the highly confined conformational space. Furthermore, we show that some fundamental questions in protein assembly can be approached applying the template concept. Using covalent template trapping of self-associated peptide assemblies in aqueous solution the structural and physical forces guiding protein folding, supramolecular assembly and molecular recognition processes can be studied on a molecular level.
Tuchscherer
G
G
Institute of Organic Chemistry, University of Lausanne, Switzerland. gabriele.tuchscherer@ico.unil.ch
Grell
D
D
Mathieu
M
M
Mutter
M
M
D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D013058:Mass Spectrometry; D008958:Models, Molecular; D008961:Models, Structural; D014176:Protein Biosynthesis; D015202:Protein Engineering / Q000379:methods*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000138:chemical synthesis / Q000737:chemistry; D013329:Structure-Activity Relationship; D013698:Templates, Genetic; D016335:Zinc Fingers
D011506:Proteins