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Taxonomic group: bacteria / Proteobacteria (Phylum: Proteobacteria)
Host organism: Homo sapiens
Associated disease: bacillary dysentery (shigellosis) [ICD11: 1A02

, ICD11: SA56

, ICD11: XN7HG

]; infection due to Shigella sonnei [ICD11: XN9M9

]

NCBI PubMed ID: 19346477
Journal NLM ID: 7505876
Publisher: National Academy of Sciences
Correspondence: robbinsjo

mail.nih.gov
Institutions: National Institute of Child Health and Human Development, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD, USA

Shigellosis, an enteric disease, is on the World Health Organization's priority prevention list. In one study, the Shigella sonnei O-specific polysaccharide (O-SP)-protein conjugate showed 72% protection against disease in Israeli army recruits exposed to high rates (8-14%) of infection. The protection was related to vaccine-induced IgG anti-O-SP levels. Synthetic oligosaccharides of Shigella dysenteriae type 1, bound by their reducing ends to a carrier protein ('sun'-type configuration), induced significantly higher antibody levels than the native O-SP bound to protein by multiple-point attachments ('lattice'-type configuration). Attempts to synthesize the S. sonnei O-SP based oligosaccharides were not successful. Here, we describe the isolation, characterization, and conjugation of low-molecular-mass O-SP-core (O-SPC) fragments. The O-SPC fragments were bound by their reducing ends similar to the preparation of the synthetic S. dysenteriae type 1 conjugates. The O-SPC conjugates used oxime linkages between the terminal Kdo residues at the reducing ends of the S. sonnei saccharides and aminooxy linkers bound to BSA or a recombinant diphtheria toxin. The coupling reaction was carried out at a neutral pH and room temperature. IgG antibody levels induced in young outbred mice by the S. sonnei O-SPC conjugates were significantly higher then those elicited by the O-SP conjugates. Accordingly, we propose to evaluate clinically these conjugates.

Lipopolysaccharide, Kdo, IgG, vaccine, glycoconjugate

Structure type: oligomer
Location inside paper: p.7975, scheme 1
Compound class: core oligosaccharide with two O-units
Contained glycoepitopes: IEDB_120354,IEDB_123890,IEDB_130650,IEDB_130670,IEDB_131186,IEDB_133751,IEDB_135818,IEDB_136906,IEDB_137472,IEDB_140088,IEDB_141794,IEDB_141807,IEDB_142345,IEDB_142488,IEDB_144998,IEDB_146664,IEDB_151528,IEDB_151531,IEDB_153543,IEDB_190606,IEDB_2189047,IEDB_226811,IEDB_983931,SB_192,SB_7

Methods: 13C NMR, 1H NMR, SDS-PAGE, ELISA, MALDI-TOF MS, serological methods, statistical analysis
Biological activity: serological data

NCBI Taxonomy refs (TaxIDs): 216599
Reference(s) to other database(s): GTC:G64710YO
Show glycosyltransferases

NMR conditions: in D2O at 308 K [as TSV]

13C NMR data:
Linkage	Residue	C1	C2	C3	C4	C5	C6
5,3,3,3,2,2	aDGalp	96.7	69.4	70.5	70.5	72.5	?
5,3,3,3,2	aDGalp	92.5	73.5	69.3	70.4	72.4	?
5,3,3,3,3,3,3,4,3,2	Ac
5,3,3,3,3,3,3,4,3	aLAltpNA	102.1	52.5	69.1	69.9	78.4	175.1
5,3,3,3,3,3,3,4,2	Ac
5,3,3,3,3,3,3,4	bDFucpN4N	104.2	52.1	77.0	56.1	68.3	16.7
5,3,3,3,3,3,3,2	Ac
5,3,3,3,3,3,3	aLAltpNA	102.3	52.4	68.9	78.3	78.1	174.7
5,3,3,3,3,3,2	Ac
5,3,3,3,3,3	bDFucpN4N	102.8	52.6	77.0	55.9	68.3	16.7
5,3,3,3,3	bDGlcp	103.7	74.0	85.4	69.3	76.7	61.4
5,3,3,3	aDGlcp	95.7	73.8	79.0	69.0	72.5	62.3
5,3,3	aDGlcp	101.6	71.6	77.4	71.6	73.4	?
5,3,4	P
5,3,7,7	%aDGlcpN
5,3,7	aXLDmanHepp
5,3	aXLDmanHepp
5,4,0	%xXEtN
5,4	%xXP?
5	aXLDmanHepp
	?XKdo?


1H NMR data:
Linkage	Residue	H1	H2	H3	H4	H5	H6
5,3,3,3,2,2	aDGalp	5.33	3.86	3.98	4.00	4.12	?
5,3,3,3,2	aDGalp	5.62	3.99	4.21	4.01	4.13	?
5,3,3,3,3,3,3,4,3,2	Ac
5,3,3,3,3,3,3,4,3	aLAltpNA	4.90	4.00	3.69	4.40	4.52	-
5,3,3,3,3,3,3,4,2	Ac
5,3,3,3,3,3,3,4	bDFucpN4N	4.76	3.88	4.19	3.96	4.08	1.34
5,3,3,3,3,3,3,2	Ac
5,3,3,3,3,3,3	aLAltpNA	4.79	3.84	3.76	4.47	4.60	-
5,3,3,3,3,3,2	Ac
5,3,3,3,3,3	bDFucpN4N	4.77	3.84	4.19	3.86	4.08	1.34
5,3,3,3,3	bDGlcp	4.74	3.40	3.70	3.50	3.45	3.78-3.90
5,3,3,3	aDGlcp	5.83	3.89	4.19	3.58	4.13	3.75-3.75
5,3,3	aDGlcp	5.28	3.68	4.06	3.79	3.86	?
5,3,4	P
5,3,7,7	%aDGlcpN
5,3,7	aXLDmanHepp
5,3	aXLDmanHepp
5,4,0	%xXEtN
5,4	%xXP?
5	aXLDmanHepp
	?XKdo?


1H/13C HSQC data:
Linkage	Residue	C1/H1	C2/H2	C3/H3	C4/H4	C5/H5	C6/H6
5,3,3,3,2,2	aDGalp	96.7/5.33	69.4/3.86	70.5/3.98	70.5/4.00	72.5/4.12	?/?
5,3,3,3,2	aDGalp	92.5/5.62	73.5/3.99	69.3/4.21	70.4/4.01	72.4/4.13	?/?
5,3,3,3,3,3,3,4,3,2	Ac
5,3,3,3,3,3,3,4,3	aLAltpNA	102.1/4.90	52.5/4.00	69.1/3.69	69.9/4.40	78.4/4.52	
5,3,3,3,3,3,3,4,2	Ac
5,3,3,3,3,3,3,4	bDFucpN4N	104.2/4.76	52.1/3.88	77.0/4.19	56.1/3.96	68.3/4.08	16.7/1.34
5,3,3,3,3,3,3,2	Ac
5,3,3,3,3,3,3	aLAltpNA	102.3/4.79	52.4/3.84	68.9/3.76	78.3/4.47	78.1/4.60	
5,3,3,3,3,3,2	Ac
5,3,3,3,3,3	bDFucpN4N	102.8/4.77	52.6/3.84	77.0/4.19	55.9/3.86	68.3/4.08	16.7/1.34
5,3,3,3,3	bDGlcp	103.7/4.74	74.0/3.40	85.4/3.70	69.3/3.50	76.7/3.45	61.4/3.78-3.90
5,3,3,3	aDGlcp	95.7/5.83	73.8/3.89	79.0/4.19	69.0/3.58	72.5/4.13	62.3/3.75-3.75
5,3,3	aDGlcp	101.6/5.28	71.6/3.68	77.4/4.06	71.6/3.79	73.4/3.86	?/?
5,3,4	P
5,3,7,7	%aDGlcpN
5,3,7	aXLDmanHepp
5,3	aXLDmanHepp
5,4,0	%xXEtN
5,4	%xXP?
5	aXLDmanHepp
	?XKdo?

¹H NMR data:

Linkage	Residue	H1	H2	H3	H4	H5	H6
5,3,3,3,2,2	aDGalp	5.33	3.86	3.98	4.00	4.12	?
5,3,3,3,2	aDGalp	5.62	3.99	4.21	4.01	4.13	?
5,3,3,3,3,3,3,4,3,2	Ac
5,3,3,3,3,3,3,4,3	aLAltpNA	4.90	4.00	3.69	4.40	4.52
5,3,3,3,3,3,3,4,2	Ac
5,3,3,3,3,3,3,4	bDFucpN4N	4.76	3.88	4.19	3.96	4.08	1.34
5,3,3,3,3,3,3,2	Ac
5,3,3,3,3,3,3	aLAltpNA	4.79	3.84	3.76	4.47	4.60
5,3,3,3,3,3,2	Ac
5,3,3,3,3,3	bDFucpN4N	4.77	3.84	4.19	3.86	4.08	1.34
5,3,3,3,3	bDGlcp	4.74	3.40	3.70	3.50	3.45	3.78 3.90
5,3,3,3	aDGlcp	5.83	3.89	4.19	3.58	4.13	3.75 3.75
5,3,3	aDGlcp	5.28	3.68	4.06	3.79	3.86	?
5,3,4	P
5,3,7,7	%aDGlcpN
5,3,7	aXLDmanHepp
5,3	aXLDmanHepp
5,4,0	%xXEtN
5,4	%xXP?
5	aXLDmanHepp
	?XKdo?

¹³C NMR data:

Linkage	Residue	C1	C2	C3	C4	C5	C6
5,3,3,3,2,2	aDGalp	96.7	69.4	70.5	70.5	72.5	?
5,3,3,3,2	aDGalp	92.5	73.5	69.3	70.4	72.4	?
5,3,3,3,3,3,3,4,3,2	Ac
5,3,3,3,3,3,3,4,3	aLAltpNA	102.1	52.5	69.1	69.9	78.4	175.1
5,3,3,3,3,3,3,4,2	Ac
5,3,3,3,3,3,3,4	bDFucpN4N	104.2	52.1	77.0	56.1	68.3	16.7
5,3,3,3,3,3,3,2	Ac
5,3,3,3,3,3,3	aLAltpNA	102.3	52.4	68.9	78.3	78.1	174.7
5,3,3,3,3,3,2	Ac
5,3,3,3,3,3	bDFucpN4N	102.8	52.6	77.0	55.9	68.3	16.7
5,3,3,3,3	bDGlcp	103.7	74.0	85.4	69.3	76.7	61.4
5,3,3,3	aDGlcp	95.7	73.8	79.0	69.0	72.5	62.3
5,3,3	aDGlcp	101.6	71.6	77.4	71.6	73.4	?
5,3,4	P
5,3,7,7	%aDGlcpN
5,3,7	aXLDmanHepp
5,3	aXLDmanHepp
5,4,0	%xXEtN
5,4	%xXP?
5	aXLDmanHepp
	?XKdo?

The spectrum also has 3 signals at unknown positions (not plotted).

There are 2 chemically distinct structures. Please, select:

CC(=O)N[C@H]1[C@H](O[C@H]2[C@H](C(=O)O)O[C@@H](O[C@H]3[C@@H](N)[C@@H](C)O[C@@H](O[C@@H]4[C@@H](O)[C@H](O[C@H]5[C@H](O)[C@@H](CO)O[C@H](O[C@H]6[C@H](O)[C@@H](CO)O[C@H](O[C@@H]7[C@H](O)[C@@H](O[C@@H]8[C@H](O)[C@@H](O[C@@H]9[C@H](O)CC(O)(C(=O)O)O[C@@H]9[C@H](O)CO)O[C@H]([C@@H](O)CO)[C@H]8OP(=O)(O)OCCN)O[C@H]([C@@H](O)CO[C@H]8O[C@H]([C@@H](O)CO[C@H]9O[C@H](CO)[C@@H](O)[C@H](O)[C@H]9N)[C@@H](O)[C@H](O)[C@@H]8O)[C@H]7OP(=O)(O)O)[C@@H]6O)[C@@H]5O[C@H]5O[C@H](CO)[C@H](O)[C@H](O)[C@H]5O[C@H]5O[C@H](CO)[C@H](O)[C@H](O)[C@H]5O)O[C@H](CO)[C@H]4O)[C@@H]3NC(C)=O)[C@H](NC(C)=O)[C@H]2O)O[C@H](C)[C@H](N)[C@@H]1O[C@@H]1O[C@@H](C(=O)O)[C@H](O)[C@H](O)[C@H]1NC(C)=O

SVG MW SMILES 3D mol Ionize