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Updated: Nov 21, 2025

The Application of Open Searching-based Approaches for the Identification of Acinetobacter baumannii O-linked Glycopeptides
Published on: November 2, 2021
Chemical Synthesis and Biological Applications of O-GlcNAcylated Peptides and Proteins
Jessica M Groenevelt1, Daniel J Corey1, Charlie Fehl1
1Department of Chemistry, Wayne State University, 5101 Cass Avenue, Detroit, MI, 48202, USA.
Abstract:
All human cells use O-GlcNAc protein modifications (O-linked N-acetylglucosamine) to rapidly adapt to changing nutrient and stress conditions through signaling, epigenetic, and proteostasis mechanisms. A key challenge for biologists in defining precise roles for specific O-GlcNAc sites is synthetic access to homogenous isoforms of O-GlcNAc proteins, a result of the non-genetically templated, transient, and heterogeneous nature of O-GlcNAc modifications. Toward a solution, this review details the state of the art of two strategies for O-GlcNAc protein modification: advances in "bottom-up" O-GlcNAc peptide synthesis and direct "top-down" installation of O-GlcNAc on full proteins. We also describe key applications of synthetic O-GlcNAc peptide and protein tools as therapeutics, biophysical structure-function studies, biomarkers, and as disease mechanistic probes to advance translational O-GlcNAc biology.
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