title: GM3, GM2 and GM1 mimics designed for biosensing: chemoenzymatic synthesis, target affinities and 900 MHz NMR analysis.
abstract: Undec-10-enyl, undec-10-ynyl and 11-azidoundecyl glycoside analogues corresponding to the oligosaccharides of human gangliosides GM3, GM2 and GM1 were synthesized in high yields using glycosyltransferases from Campylobacter jejuni. Due to poor water solubility of the substrates, the reactions were carried out in methanol-water media, which for the first time were shown to be compatible with the C. jejuni alpha-(2-->3)-sialyltransferase (CST-06) and beta-(1-->4)-N-acetylgalactosaminyltransferase (CJL-30). Bioequivalence of our synthetic analogues and natural gangliosides was examined by binding to Vibrio cholerae toxin and to the B subunit of Escherichia coli heat-labile enterotoxin. This bioequivalence was confirmed by binding mouse and human monoclonal antibodies to GM1 and acute phase sera containing IgM and IgG antibodies to GM1 from patients with the immune-mediated polyneuropathy Guillain-Barré syndrome. The synthesized compounds were analyzed by 1D and 2D 900 MHz NMR spectroscopy. TOCSY and DQF-COSY experiments in combination with 13C-1H correlation measurements (HSQC, HMBC) were carried out for primary structural characterization, and a complete assignment of all 1H and 13C chemical shifts is presented.
authors.affiliation: Laboratory of Organic Chemistry, Wageningen University, Dreijenplein 8, 6703 HB, Wageningen, The Netherlands.
authors.forename: Aliaksei V
authors.initials: AV
authors.lastname: Pukin
authors.forename: Carel A G M
authors.initials: CA
authors.lastname: Weijers
authors.forename: Barend
authors.initials: B
authors.lastname: van Lagen
authors.forename: Rainer
authors.initials: R
authors.lastname: Wechselberger
authors.forename: Bin
authors.initials: B
authors.lastname: Sun
authors.forename: Michel
authors.initials: M
authors.lastname: Gilbert
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Karwaski
authors.forename: Dion E A
authors.initials: DE
authors.lastname: Florack
authors.forename: Bart C
authors.initials: BC
authors.lastname: Jacobs
authors.forename: Anne P
authors.initials: AP
authors.lastname: Tio-Gillen
authors.forename: Alex
authors.initials: A
authors.lastname: van Belkum
authors.forename: Hubert P
authors.initials: HP
authors.lastname: Endtz
authors.forename: Gerben M
authors.initials: GM
authors.lastname: Visser
authors.forename: Han
authors.initials: H
authors.lastname: Zuilhof
mesh_terms: D000818:Animals; D040761:Biomimetic Materials / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D015374:Biosensing Techniques; D016123:Campylobacter jejuni / Q000201:enzymology; D002417:Cattle; D002772:Cholera Toxin / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005690:Galactose / Q000737:chemistry; D005732:Gangliosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D005947:Glucose / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011956:Receptors, Cell Surface / Q000378:metabolism
chemical_list: D005732:Gangliosides; D011956:Receptors, Cell Surface; C034993:ganglioside receptor; D002772:Cholera Toxin; D005947:Glucose; D005690:Galactose