Work

Anomeric Fatty Acid Functionalization Prevents Nonenzymatic S-Glycosylation by Monosaccharide Metabolic Chemical Reporters

Year: 2021

Type: article

Abstract: Metabolic chemical reports have fundamentally changed the way researchers study glycosylation. However, when administered as per- O -acetylated sugars, reporter molecules can participate in nonspecific chemical labeling of cysteine residues termed S -glycosylation. Without detailed proteomic analyses, these labeling events can be indistinguishable from bona fide enzymatic labeling convoluting experimental results. Here, we report a solution in the synthesis and characterization of two reporter molecules functionalized at the anomeric position with hexanoic acid: 1-Hex-GlcNAlk and 1-Hex-6AzGlcNAc. Both reporters exhibit robust labeling over background with negligible amounts of nonspecific chemical labeling in cell lysates. This strategy serves as a template for the design of future reporter molecules allowing for more reliable interpretation of results.

Source: ACS Chemical Biology

DOI: 10.1021/acschembio.1c00470

Authors: Nichole J. Pedowitz, Emma G. Jackson, Justin M. Overhulse, Charles E. McKenna, Jennifer J. Kohler, Matthew R. Pratt

Institutions: University of Southern California, The University of Texas Southwestern Medical Center

Language: English

Topic: Click Chemistry and Applications

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: green

Funders: Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases