Taxonomic group: bacteria / Proteobacteria
(Phylum: Proteobacteria)
Host organism: Homo sapiens
Associated disease: infection due to Escherichia coli [ICD11:
XN6P4 
]
NCBI PubMed ID: 22855025Publication DOI: 10.1039/c2ob26105gJournal NLM ID: 101154995Publisher: The Royal Society of Chemistry
Correspondence: mnitz
chem.utoronto.ca
Institutions: Department of Chemistry, University of Toronto, Toronto, Ontario, Canada, Program in Molecular Structure and Function, The Hospital of Sick Children and Department of Biochemistry, University of Toronto, Ontario M5G 1X8, Canada
Many medically important biofilm forming bacteria produce similar polysaccharide intercellular adhesins (PIA) consisting of partially de-N-acetylated β-(1→6)-N-acetylglucosamine polymers (dPNAG). In Escherichia coli, de-N-acetylation of the β-(1→6)-N-acetylglucosamine polymer (PNAG) is catalysed by the carbohydrate esterase family 4 deacetylase PgaB. The de-N-acetylation of PNAG is essential for productive PNAG-dependent biofilm formation. Here, we describe the development of a fluorogenic assay to monitor PgaB activity in vitro and the synthesis of a series of PgaB inhibitors. The synthesized inhibitors consist of a metal chelating functional group on a glucosamine scaffold to target the active site metal ion of PgaB. Optimal inhibition was observed with N-thioglycolyl amide (K(i) = 480 muM) and N-methyl-N-glycolyl amide (K(i) = 320 muM) glucosamine derivatives. A chemoenzymatic synthesis of an N-thioglycolyl amide PNAG pentasaccharide led to an inhibitor with an improved K(i) of 280 muM.
synthesis, Escherichia coli, adhesin, biofilms, PNAG, inhibitor, PIA
Structure type: oligomer
Location inside paper: p.7106, scheme 4, 32
Trivial name: N-thioglycolyl amide PNAG pentasaccharide
Contained glycoepitopes: IEDB_135813,IEDB_137340,IEDB_141807,IEDB_151531
Methods: 1H NMR, chemical synthesis, chemical methods, biochemical methods
Biological activity: inhibition of PgaB data
Enzymes that release or process the structure: PgaB de-N-acetylase
Synthetic data: chemical and chemoenzymatic
Comments, role: one of inhibitors of PgaB
Related record ID(s): 29938
NCBI Taxonomy refs (TaxIDs): 562
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There is only one chemically distinct structure:
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