Angewandte Chemie International Edition in English · 1989 · 404 citations · 212 references
Life SciencesBiochemistryMolecular BiologyProtein EngineeringProtein FoldingSynthetic BiologyMacromolecular AssemblyProtein DesignProtein Folding PathwaysProtein StructureFolding PathwaysMacromolecule SynthesisStructure-based Protein DesignStructure-guided Protein Engineering
Abstract Advances in methodology in both chemistry and molecular biology allow us to take a fresh look at protein science. Chemical synthesis of peptides and site‐directed mutagenesis are now standard research tools, paving the way for the construction of new proteins with tailor‐made structural and functional properties. The decisive hurdle on the way lies not in the synthesis of the molecules proper but rather in a better understanding of the complex folding pathways of polypeptide chains into spatially well‐defined structures. Can the chemist use his synthetic tools to bypass the notorious “folding problem?” In this article, we present a new approach developed in our laboratory, which opens a chemical route to artificial proteins with predetermined three‐dimensional structures, allowing a first step towards the synthesis of new proteins with functional properties.
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