Metal‐Chelating Amino Acids As Building Blocks For Synthetic Receptors Sensing Metal Ions And Histidine‐Tagged Proteins

Abstract

Protein structure and function rely on a still not fully understood interplay of energetic and entropic constraints defined by the permutation of the twenty genetically encoded amino acids. Many attempts have been undertaken to design peptide-peptide interaction pairs and synthetic receptors de novo by using this limited number of building blocks. We describe a rational approach to creating a building block based on a tailored metal-chelating amino acid. Nepsilon,Nepsilon-bis(carboxymethyl)-L-lysine can be flexibly introduced into peptides by 9-fluorenylmethoxycarbonyl solid-phase chemistry. The corresponding metal-chelating peptides act as metal sensors and synthetic receptors for histidine-tagged proteins. These biochemical tweezers will open new ways to control protein-protein interactions, to design peptide-based interaction pairs, or to generate switchable protein function.