Expanding the Scope of Biocatalysis: Oxidative Biotransformations on Solid‐Supported Substrates

Abstract

Oxidative biocatalytic reactions were performed on solid-supported substrates, thus expanding the repertoire of biotransformations that can be carried out on the solid phase. Various phenylacetic and benzoic acid analogs were attached to controlled pore glass beads via an enzyme-cleavable linker. Reactions catalyzed by peroxidases (soybean and chloro), tyrosinase, and alcohol oxidase/dehydrogenase gave a range of products, including oligophenols, halogenated aromatics, catechols, and aryl aldehydes. The resulting products were recovered following cleavage from the beads using α-chymotrypsin to selectively hydrolyze a chemically non-labile amide linkage. Controlled pore glass (CPG) modified with a polyethylene glycol (PEG) linker afforded substantially higher product yields than non-PEGylated CPG or non-swellable polymeric resins. This work represents the first attempt to combine solid-phase oxidative biotransformations with subsequent protease-catalyzed cleavage, and serves to further expand the use of biocatalysis in synthetic and medicinal chemistry.

Redox Reactions Catalyzed by Isolated Enzymes

“…236 Tyrosinases as well as other oxidoreductases have been exploited for the selective modification of solid-supported substrates, expanding the repertoire of biotransformations that can be carried out in the solid phase. 237 Finally, it deserves to be mentioned the tyrosinase-catalyzed cleavage of amino acid phenylhydrazides, which has been proposed as a very mild and selective method for the C-terminal deprotection of peptides (Figure 35). 238…”

“…Worth noting is also the synthesis of specifically deuterated, tritiated, or 14 C-labeled isotopomers of l -DOPA from the corresponding l -tyrosine derivatives . Tyrosinases as well as other oxidoreductases have been exploited for the selective modification of solid-supported substrates, expanding the repertoire of biotransformations that can be carried out in the solid phase …”

Combining triazole ligation and enzymatic glycosylation on solid phase simplifies the synthesis of very long glycoprotein analogues

“…Although our first assay gave encouraging results, we nevertheless found enzymatic glycosylation of supported peptide 10a to be much less efficient than a solution phase control experiment. However, satisfactory results were obtained by introducing a 3000 Da PEG spacer between the peptide and the solid support 22 ( 10c ): after peptide release, LC-MS analysis showed a mixture mainly composed of pentaglycosylated ( 11f ) and hexaglycosylated ( 11g ) peptides, with a product distribution comparable to that obtained in solution (ESI, Tables S6–S8 † ). 23 Only very low amounts (<2%) of compounds containing more than six α-GalNAc could be detected in the mixture.…”

Characterization of immobilized tyrosinase – an enzyme that is stable in organic solvent at 100 °C

“…Compared with the covalent bonding, 28,29 entrapment, 30-32 copolymerization 33,34 and encapsulation methods, [35][36][37] the conditions of the adsorption method are much milder than the other methods. Furthermore, the glass beads, 38,39 graphene, 40,41 magnetic nanoparticles 42 and metal-organic frameworks (MOFs) 43,44 were chosen as the supports to immobilize the enzyme in previous study. In this study, the biocompatible polymers (i.e.…”