De Novo Designed α‐Helical Coiled‐Coil Peptides as Scaffolds for Chemical Reactions

• Published in: Chemistry : a European journal Vol. 25; no. 7; pp. 1665 - 1677
• Main Authors: Rink, W. Mathis, Thomas, Franziska
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.02.2019
• Subjects: Autocatalysis; Biology; Building design; Catalysts; Chemical reactions; Chemistry; coiled coil; Coils; de novo design; Design; enzyme; Organic chemistry; Peptides; Protein folding; Proteins; proximity-induced reactions; reaction scaffold; Redox reactions; Scaffolds; Stability; enzyme; de novo design; reaction scaffold; proximity-induced reactions; coiled coil
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201802849

Coiled coils (CCs) are well‐understood protein‐folding motifs. They appear in a variety of oligomer states and as homo‐ and heteromeric assemblies. This versatility and the general accessibility by de novo design makes them ideal building blocks for synthetic biology. This Minireview highlights the efforts being made in designing small peptide catalysts or reaction templates based on the CC scaffold. The first reports described autocatalysis or mediation of peptide ligation based on CC recognition. Over the years, the designs became more advanced, catalyzing ester hydrolysis, acyl transfer and redox reactions with partial enzyme‐like reactivity. Due to the ability to control CC assembly, and, in heterodimeric systems, the association and dissociation, the CC motif has become a common peptide tag in chemical biology. Round and round they go! The de novo design strategies of peptide catalysts and reaction templates based on the well‐understood coiled‐coil folding motif are summarized. Coiled‐coil dimers to heptamers were used to mimic enzymatic reactions, such as peptide ligations, transfer reactions, ester hydrolysis and redox reactions. Furthermore, coiled‐coil mediated covalent fluorescence labelling of proteins is discussed.