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

Abstract

Funding information JSPSGrants-in-Aid for SpeciallyPromotedResearch,Grant/AwardNumber: JP19H05461; ScientificResearch (B), Grant/AwardNumber: JP19H02697; JST PRESTO,Grant/AwardNumber: JPMJPR20A7 Abstract: Short peptideswith sequences of alternating Land 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 bundleof twoantiparallelβ-helices. These results demonstrate thatmetal coordination can induce even as-yet unrecognized structures in the folding and assembly pathways of short peptides.