Metallopeptide catalysts and artificial metalloenzymes containing unnatural amino acids

Abstract

Metallopeptide catalysts and artificial metalloenzymes built from peptide scaffolds and catalytically active metal centers possess a number of exciting properties that could be exploited for selective catalysis. Control over metal catalyst secondary coordination spheres, compatibility with library based methods for optimization and evolution, and biocompatibility stand out in this regard. A wide range of unnatural amino acids have been incorporated into peptide and protein scaffolds using several distinct methods, and the resulting unnatural amino acid containing scaffolds can be used to create novel hybrid metal-peptide catalysts. Promising levels of selectivity have been demonstrated for several hybrid catalysts, and these provide a strong impetus and important lessons for the design of and optimization of hybrid catalysts.

d‐Cysteine Ligands Control Metal Geometries within De Novo Designed Three‐Stranded Coiled Coils

“…[12,16,[29][30][31][32][33][34][35] d-Amino acids, for example, have been exploited in the design to change the chemical and physicalp roperties of engineeredp rotein structures. [5,12,29,[34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51] This expands the capability for engineering proteins with improved efficiency or novelf unctions as compared to natural systems.…”

An internal electron reservoir enhances catalytic CO2 reduction by a semisynthetic enzyme

“…Diverse approaches have been employed to generate these engineered systems, including cofactor substitution, 14 modification of an existing scaffold, and attachment of an unnatural moiety to a protein, 15-17 and there are many successful examples in which new functionality has been introduced into noncatalytic proteins. This approach often provides a straightforward route to tune the reactivity of a system, enabling novel chemical processes or benign reaction conditions that have otherwise been difficult to accomplish.…”

Design and engineering of artificial oxygen-activating metalloenzymes

“…77,309 UAAs are now routinely being incorporated into peptides and proteins to enable functions beyond those accessible using natural amino acids. 310-314 UAAs have been used to enable new modes of metal coordination or covalent attachment, which has led to construction of several new artificial metalloenzymes and metallopeptides not possible using natural amino acids.…”