The Construction of New Proteins. Part III. Artificial folding units by assembly of amphiphilic secondary structures on a template

Abstract

Abstract A new general strategy for the construction of artificial proteins with predetermined tertiary structure is presented. Amphiphilic α‐helix and β‐sheet‐forming oligopeptides are assembled on a multifunctional ttemplate molecule which directs the peptide blocks to adopt characteristic folding topologies. The design, synthesis, and conformational properties of these template‐assembled synthetic proteins (TASP) are exemplified for βαβ‐, α‐helix‐bundle‐ and β‐barrel‐like tertiary structures using specially designed oligopeptides as template molecules. In contrast to linear polypeptide chains of comparable molecular weights, these conceptually novel marcromolecules are readily accessible to chemical synthesis and exhibit excellent solubility in a number of solvents. Experimental evidence is provided for a template‐induced intramolecular folding to secondary and tertiary structures in aqueous solutions. This approach opens new prospects for the chemical construction of biomacromolecules with tailormade structural and functional properties.