title: Development of Rare Bacterial Monosaccharide Analogs for Metabolic Glycan Labeling in Pathogenic Bacteria.
abstract: Bacterial glycans contain rare, exclusively bacterial monosaccharides that are frequently linked to pathogenesis and essentially absent from human cells. Therefore, bacterial glycans are intriguing molecular targets. However, systematic discovery of bacterial glycoproteins is hampered by the presence of rare deoxy amino sugars, which are refractory to traditional glycan-binding reagents. Thus, the development of chemical tools that label bacterial glycans is a crucial step toward discovering and targeting these biomolecules. Here, we explore the extent to which metabolic glycan labeling facilitates the studying and targeting of glycoproteins in a range of pathogenic and symbiotic bacterial strains. We began with an azide-containing analog of the naturally abundant monosaccharide N-acetylglucosamine and discovered that it is not broadly incorporated into bacterial glycans, thus revealing a need for additional azidosugar substrates to broaden the utility of metabolic glycan labeling in bacteria. Therefore, we designed and synthesized analogs of the rare deoxy amino d-sugars N-acetylfucosamine, bacillosamine, and 2,4-diacetamido-2,4,6-trideoxygalactose and established that these analogs are differentially incorporated into glycan-containing structures in a range of pathogenic and symbiotic bacterial species. Further application of these analogs will refine our knowledge of the glycan repertoire in diverse bacteria and may find utility in treating a variety of infectious diseases with selectivity.
authors.affiliation: Department of Chemistry & Biochemistry, Bowdoin College , 6600 College Station, Brunswick, Maine 04011, United States.
authors.forename: Emily L
authors.initials: EL
authors.lastname: Clark
authors.affiliation: Department of Chemistry, Indian Institute of Technology Bombay , Powai, Mumbai, 400076, India.
authors.forename: Madhu
authors.initials: M
authors.lastname: Emmadi
authors.affiliation: Department of Chemistry & Biochemistry, Bowdoin College , 6600 College Station, Brunswick, Maine 04011, United States.
authors.forename: Katharine L
authors.initials: KL
authors.lastname: Krupp
authors.affiliation: Department of Chemistry, Indian Institute of Technology Bombay , Powai, Mumbai, 400076, India.
authors.forename: Ananda R
authors.initials: AR
authors.lastname: Podilapu
authors.affiliation: Department of Chemistry & Biochemistry, Bowdoin College , 6600 College Station, Brunswick, Maine 04011, United States.
authors.forename: Jennifer D
authors.initials: JD
authors.lastname: Helble
authors.affiliation: Department of Chemistry, Indian Institute of Technology Bombay , Powai, Mumbai, 400076, India.
authors.forename: Suvarn S
authors.initials: SS
authors.lastname: Kulkarni
authors.affiliation: Department of Chemistry & Biochemistry, Bowdoin College , 6600 College Station, Brunswick, Maine 04011, United States.
authors.forename: Danielle H
authors.initials: DH
authors.lastname: Dube
mesh_terms: D001386:Azides / Q000737:chemistry* / Q000378:metabolism; D001419:Bacteria / Q000737:chemistry* / Q000378:metabolism; D001424:Bacterial Infections / Q000382:microbiology; D001426:Bacterial Proteins / Q000032:analysis* / Q000378:metabolism; D015153:Blotting, Western; D005643:Fucose / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D006023:Glycoproteins / Q000032:analysis* / Q000378:metabolism; D006595:Hexosamines / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D060847:Metabolic Engineering; D011135:Polysaccharides, Bacterial / Q000032:analysis* / Q000378:metabolism; D013194:Staining and Labeling
chemical_list: D001386:Azides; D001426:Bacterial Proteins; D006023:Glycoproteins; D006595:Hexosamines; D011135:Polysaccharides, Bacterial; D005643:Fucose; C059377:N-acetylfucosamine; C013920:4-deoxyneosamine C