Taxonomic group: bacteria / Proteobacteria
(Phylum: Proteobacteria)
Host organism: Homo sapiens
Associated disease: bacillary dysentery [ICD11:
1A02 
, ICD11:
XN7HG ];
infection due to Shigella flexneri [ICD11:
XN7Y2 ]
NCBI PubMed ID: 19467535Publication DOI: 10.1016/j.carres.2009.03.029Journal NLM ID: 0043535Publisher: Elsevier
Correspondence: B.M.Pinto <bpinto
sfu.ca>
Institutions: Department of Chemistry, Simon Fraser University, Burnaby, BC, Canada V5A 1S6, Institute of Elemento-organic Chemistry and Department of Chemical Biology, Nankai University, Tianjin, China
Two glycopeptide chimeras corresponding to the Shigella flexneri Y O-polysaccharide and its peptide mimic were designed in an attempt to improve the binding affinity by increasing the entropy of binding relative to the original octapeptide mimic of the O-polysaccharide. The design was based on the X-ray crystal structures of a monoclonal antibody SYA/J6 in complex with its cognate ligands, a pentasaccharide corresponding to the S. flexneri Y O-polysaccharide and the octapeptide mimic, MDWNMHAA. Both chimeric molecules consist of a rhamnose trisaccharide linked through an α- or β-thioglycosidic linkage to a MDW moiety in which the W unit has been modified. We predicted that omission of the NMHAA moiety would obviate the bound water molecules that provided complementarity with the antibody-combining site, and the conformational restriction resulting from imposition of an alpha-turn at the C-terminus of the peptide. The glycopeptides were then docked into the active site of SYA/J6 using the program autodock 3.0, and the structures were optimized. The best models obtained in each case showed that the chimeric molecules, with either an α- or β-thioglycosidic linkage, might be reasonable surrogate ligands for the antibody. We report here the synthesis of the alpha-glycopeptide employing solution and solid-phase strategies. Immunochemical characterization indicated that the alpha-glycopeptide unfortunately did not inhibit binding of SYA/J6 to the S. flexneri Y lipopolysaccharide.
synthesis, molecular modeling, immunochemistry, Shigella flexneri Y O-polysaccharide, carbohydrate-mimetic peptide, glycopeptide chimera
Structure type: polymer chemical repeating unit
Location inside paper: p.1413, fig.1a
Compound class: O-polysaccharide, O-antigen, Shigella serogroup Y antigen, rhamnoglucan
Contained glycoepitopes: IEDB_125613,IEDB_125614,IEDB_127514,IEDB_133752,IEDB_133753,IEDB_133754,IEDB_135813,IEDB_135849,IEDB_136105,IEDB_137340,IEDB_141807,IEDB_141815,IEDB_141816,IEDB_143253,IEDB_151531,IEDB_153213,IEDB_225177,IEDB_885823
Methods: 13C NMR, 1H NMR, NMR-2D, X-ray, ELISA, chemical synthesis, MALDI-TOF MS, NMR-1D, LSI-MS, immunochemical methods, molecular modeling
Synthetic data: synthesis
3D data: 3D data
Related record ID(s): 3226, 3707, 5546, 9230, 21744, 22617, 23080, 23428, 23430, 23657, 23918, 24814, 108668, 110468, 113249, 114338, 115105, 115244, 122484, 122774, 130212, 130503, 148073, 148768
NCBI Taxonomy refs (TaxIDs): 424720Reference(s) to other database(s): GTC:G98477AV, GlycomeDB:
3543, CCSD:
2501, CBank-STR:8288, GenDB:AFl28887
Show glycosyltransferases
There is only one chemically distinct structure:
Found 
report error