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An Engineered β‐Hairpin Peptide Forming Thermostable Complexes with ZnII, NiII, and CuII through a His3 Site

2022/11/29 by Truc Lam Pham, Sunnatullo Fazliev, Philipp Baur +2 · 1 voice
Chemistry · Medicine · Biochemistry, Genetics and Molecular Biology · #Ferrocene Chemistry and Applications #Metal complexes synthesis and properties #Chemical Synthesis and Analysis

paper · pdf · doi:10.1002/cbic.202200588

openalex publication_date 2022/11/29 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01

Abstract

Abstract The three‐dimensional structure of a peptide, which determines its function, can denature at elevated temperatures, in the presence of chaotropic reagents, or in organic solvents. These factors limit the applicability of peptides. Herein, we present an engineered β‐hairpin peptide containing a His 3 site that forms complexes with Zn II , Ni II , and Cu II . Circular dichroism spectroscopy shows that the peptide−metal complexes exhibit melting temperatures up to 80 °C and remain folded in 6 M guanidine hydrochloride as well as in organic solvents. Intrinsic fluorescence titration experiments were used to determine the dissociation constants of metal binding in the nano‐ to sub‐nanomolar range. The coordination geometry of the peptide−Cu II complex was studied by EPR spectroscopy, and a distorted square planar coordination geometry with weak interactions to axial ligands was revealed. Due to their impressive stability, the presented peptide−metal complexes open up interesting fields of application, such as the development of a new class of peptide−metal catalysts for stereoselective organic synthesis or the directed design of extremophilic β‐sheet peptides.

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