De Novo Designed Copper α‐Helical Peptides: From Design to Function

Abstract

De novo protein design is a fascinating and powerful approach to the design of metal sites in the interior of simplified protein scaffolds. A series of de novo designed copper peptides are herein described. They consist of peptide constructs that possess a secondary and tertiary structure, and that can be regarded as simplified proteins from which most of the structural complexity has been removed. Although relatively small, these copper peptides retain enough complexity to show features typical of proteins, such as enzyme-like catalytic behavior or specific spectroscopic features. This review focuses on the de novo design of α-helical constructs [a] Matteo Tegoni graduated at the University of Parma, where he also obtained his Ph. D. in the field of the thermodynamics of formation of metal complexes in solution. In 2002 he was appointed Senior Research Associate in General and Inorganic Chemistry at the University of Parma, where he is teacher of General and Inorganic Chemistry. He served on the national (young chemists group) and regional boards of the Italian Chemical Society, and he is involved in the dissemination of science and chemistry in schools, and in other outreach activities for the public. His current research interests are in the fields of de novo designed metallopeptides and artificial metalloenzymes, metal-based supramolecular assemblies, and biologically relevant metal complexes.

Protein Design: Toward Functional Metalloenzymes

“…(A review on de novo designed copper-peptides was recently accepted, see ref 1004 .) Copper enzymes are involved in many important metabolic pathways and are among the most efficient biological redox catalysts.…”

De Novo Construction of Redox Active Proteins

“…Besides binding FeS clusters, Co and Ni, Cys and His groups buried in close proximity in de novo helical bundles can bind a host of other redox active metals (for a review, see Tegoni, 2014). Single-chain 4-helix bundle copper centers are promising for future in vivo work.…”

Design and engineering of a man-made diffusive electron-transport protein

“…As maquettes are about the same size as natural electron transporters and tolerate dramatic sequence and charge changes without compromising redox function, they are excellent prospects for insertion into natural electron-transfer networks to engineer novel inter-protein connections. Already, a choice of maquettes with a variety of redox cofactor types, including iron-sulfur cluster [19], flavin [21], quinone [22], copper [41] and irons [42], are available for external patterning.…”