Parallel and antiparallel peptide double β‐helices controlled by metal‐induced folding and assembly

Abstract

Abstract Short peptides with sequences of alternating l‐ and d‐residues are known to form antiparallel double β‐helical structures, but their equilibrium structures have not been characterized in detail. Here, we use metal coordination of a simple octapeptide, ‐(l‐Val‐d‐Val)4‐, modified with two coordinating side chains at the (i, j)‐th residues to uncover these elusive structures. When (i, j) = (3, 5), complexation with ZnI2 induces a parallel double β‐helix, which is not commonly seen. In contrast, when (i, j) = (5, 7), a commonly occurring antiparallel double β‐helix (Type I) is formed. Interestingly, complexation of the peptide with (i, j) = (3, 7) gives another antiparallel double β‐helix, the unknown Type II structure, which has an inverted orientation of the two strands. Complexation of a monotopic peptide (i = 3) with trans‐PdCl2 yields a Pd(II)‐linked dimeric bundle of two antiparallel β‐helices. These results demonstrate that metal coordination can induce even as‐yet unrecognized structures in the folding and assembly pathways of short peptides. Key points Structural elucidation of elusive peptide nanostructures Precise structural control of double helical molecules Fusion of peptide folding and metal‐directed self‐assembly

Keywords

• β‐helix
• coordination bonds
• folding
• peptides
• self‐assembly