ChemRxiv
These are preliminary reports that have not been peer-reviewed. They should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information. For more information, please see our FAQs.
1/1
3 files

Site-Selective Palladium-Catalyzed Oxidation of Glucose in Glycopeptides

preprint
submitted on 17.03.2021, 15:58 and posted on 18.03.2021, 13:02 by Niels R.M. Reintjens, Liubov Yakovlieva, Nittert Marinus, Johan Hekelaar, Francesca Nuti, Anna Maria Papini, Martin D. Witte, Adriaan J. Minnaard, Marthe Walvoort

Here we report a novel method of site-selective oxidation of glucose moieties on individual glycopeptides and on a mixture of tryptic glycopeptides. The organometallic catalyst [(neocuproine)PdOAc]2OTf2, that was previously shown to perform regioselective C3-oxidation of glucosides, was used in the scope of this work. The selectivity of the catalyst towards glucose and the sensitivity of specific amino acid residues to oxidation was explored by screening a select panel of glycopeptides in the oxidation reactions. We reveal that glucosylated peptides are more readily oxidized compared to galactosylated peptides, and Thr/Ser-oxidation is a concomitant side-reaction. The oxidation methodology was also applied to the complex mixture of tryptic glucopeptides that was generated from the fragment of Haemophilus influenzae adhesin glycoprotein. The resulting keto-group of the glucose was further transformed into an oxime functionality, which allows introduction of various groups of interest. The methodology outlined in this work will allow to perfrom late-stage modification of glucopeptides as well as selective oxidation and functionalization of tryptic glucopeptides for proteomics analysis.

Funding

Dutch Organization for Scientific Research (VENI 722.016.006)

European Research Council Rosalind Franklin Fellowship COFUND project 60021

Fondazione Ente Cassa di Risparmio di Firenze (Italy) (grant n. 2014/0306)

History

Email Address of Submitting Author

m.t.c.walvoort@rug.nl

Institution

University of Groningen

Country

the Netherlands

ORCID For Submitting Author

0000-0003-1101-2659

Declaration of Conflict of Interest

The authors declare no conflict of interest

Exports