Metal-chelating amino acids as building blocks for synthetic receptors sensing metal ions and histidine-tagged proteins

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 <LF>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.