In vivo catalyzed new-to-nature reactions

Abstract

Bioorthogonal chemistry largely relies on the use of abiotic metals to catalyze new-to-nature reactions in living systems. Over the past decade, metal complexes and metal-encapsulated systems such as nanoparticles have been developed to unravel the reactivity of transition metals, including ruthenium, palladium, iridium, copper, iron, and gold in biological systems. Thanks to these remarkable achievements, abiotic catalysts are able to fluorescently label cells, uncage or form cytotoxic drugs and activate enzymes in cellulo/vivo. Recently, strategies for the delivery of such catalysts to specific cell types, cell compartments or proteins were established. These studies reveal the enormous potential of this emerging field and its application in both medicinal chemistry and in synthetic biology.

Metallvermittelte Funktionalisierung natürlicher Peptide und Proteine: Biokonjugation mit Übergangsmetallen

“…Die Coumarin-haltigen Liganden an dem Goldkomplex und an Albumin sind grün bzw.blau dargestellt. Dieser Fall aus der Goldchemie ist bis heute das einzige Beispiel einer übergangsmetallvermittelten Modifikation an einem natürlichen Protein in vivo ohne gentechnische Hilfe, [219] obwohl in den entsprechenden Berichten weder Erkenntnisse über die Identitätd er modifizierten Proteine noch über deren aktive Labelingzentren vorlagen. c) Struktur des humanen Serumalbumins (HSA), das in dieser Studie zur Gewinnung des Glycoalbumins eingesetzt wurde (PDB ID:1AO6).…”

Intracellular Chemistry: Integrating Molecular Inorganic Catalysts with Living Systems

“…Unlike artificial metalloenzymes, in which their metal centers are shielded from the external environment, uncaged metal species are susceptible to coordination inhibition by biological nucleophiles such as glutathione (GSH), thiol‐containing proteins, and nucleobases. Despite the challenges of performing catalytic reactions in heterogeneous aqueous media, there have been some successes in integrating inorganic catalysts with living hosts . In this article, the acronym SIMCat (small‐molecule intracellular metal catalyst) will be used to describe non‐toxic low molecular weight metal catalysts that are active inside biological systems.…”

“…Despitet he challenges of performing catalytic reactions in heterogeneous aqueousm edia, there have been some successes in integrating inorganic catalysts with living hosts. [22] In this article, the acronym SIMCat (small-molecule intracellular metal catalyst) will be used to describe non-toxic low molecular weightm etal catalysts that are active inside biological systems. This terminology is necessary to distinguish SIMCats from macromolecular (e.g.…”

A Screening Platform to Identify and Tailor Biocompatible Small‐Molecule Catalysts

“…[2,3] Although these approaches have been traditionally considered to be incompatible, small-molecule catalysts that can interface with cellular metabolism have the potentialt oe xpand biological function without the need for genetic manipulation. [4][5][6] For example,s uch biocompatible catalysts could be parto fc ellular factories,i nw hich they perform new-to-nature transformations to diversify molecules producedby an organism. [7][8][9][10] Thus, such ac oncertede ffort of synthetic chemistry and metabolic engineering could pave the way toward the direct synthesis of value-added compounds in cellular settings.A dditionally,b iocompatible catalysis holds promise for biomedical applications, such as targeted drug release/synthesis, [11][12][13][14][15] the disruption of cell-cellc ommunication or rescuing dysfunctional enzymes involvedi nh uman diseases.…”

“…Moreover,m etabolite concentrationsa re typicallyl ow (< 1mm), compared to the standard substrate concentrationse mployed in organic synthesis. [5,6,16] Conversely, the complex intra and extracellular environments of organisms contain am yriado fc ompounds that can poison exogenously supplied catalysts or reagents. [17] Consequently, the discovery and optimization of biocompatible catalysts and reactions remain challenging.…”