Palladium-Catalyzed Oxidation of Glucose in Glycopeptides

Selective modification of carbohydrate residues in glycopeptides is highly relevant as a tool in glycobiology. In particular, oxidation allows for subsequent ligation with a label or handle and can be effectuated enzymatically or chemically. Chemical oxidation of carbohydrate residues in glycopeptides is nearly invariably done using periodate cleavage, leading to aldehydes. In this work, we applied palladium-catalyzed oxidation for the same purpose. The catalyst, [(neocuproine)PdOAc](2)OTf2, developed for the site-selective oxidation of mono- and oligosaccharides on preparative scale, proved suitable for the oxidation of glucose residues in a series of glucopeptides. Careful optimization of the reaction conditions is necessary to get acceptable conversions without excessive over-oxidation of amino acid side-chains, in particular threonine. The resulting carbonyl function can be used for an oxime-ligation to biotin. A protocol for the analysis of the products using mass spectrometry is also reported.

Automated summary

Selective modification of carbohydrate residues in glycopeptides is important in glycobiology. In this study, palladium-catalyzed oxidation was used to achieve the same purpose, and the catalyst proved suitable for the oxidation of glucose residues. Careful optimization of reaction conditions is necessary to achieve desired conversion rates and avoid excessive oxidation of amino acid side-chains. The resulting carbonyl function can be used for oxime-ligation with biotin.