title: Derivatization of a bioorthogonal protected trisaccharide linker-toward multimodal tools for chemical biology.
abstract: When cross-linking biomolecules to surfaces or to other biomolecules, the use of appropriate spacer molecules is of great importance. Mimicking the naturally occurring spacer molecules will give further insight into their role and function, possibly unveil important issues regarding the importance of the specificity of carbohydrate-based anchor moieties, in e.g., glycoproteins and glycosylphosphatidylinositols. Herein, we present the synthesis of a lactoside-based trisaccharide, potentially suitable as a heterobifunctional bioorthogonal linker molecule whereon valuable chemical handles have been conjugated. An amino-derivative having thiol functionality shows promise as novel SPR-surfaces. Furthermore, the trisaccharide has been conjugated to a cholesterol moiety in combination with a fluorophore which successfully assemble on the cell surface in lipid microdomains, possibly lipid-rafts. Finally, a Cu(I)-catalyzed azide-alkyne cycloaddition reaction (CuAAC) confirms the potential use of oligosaccharides as bioorthogonal linkers in chemical biology.
authors.affiliation: Division of Chemistry and ‡Division of Molecular Physics, IFM, Linköping University , SE-581 83 Linköping, Sweden.
authors.forename: Timmy
authors.initials: T
authors.lastname: Fyrner
authors.forename: Karin
authors.initials: K
authors.lastname: Magnusson
authors.forename: K Peter R
authors.initials: KP
authors.lastname: Nilsson
authors.forename: Per
authors.initials: P
authors.lastname: Hammarström
authors.forename: Daniel
authors.initials: D
authors.lastname: Aili
authors.forename: Peter
authors.initials: P
authors.lastname: Konradsson
mesh_terms: D000480:Alkynes / Q000737:chemistry; D001386:Azides / Q000737:chemistry; D002460:Cell Line; D002784:Cholesterol / Q000737:chemistry; D057930:Click Chemistry; D003432:Cross-Linking Reagents / Q000138:chemical synthesis* / Q000737:chemistry; D061565:Cycloaddition Reaction; D005347:Fibroblasts / Q000648:ultrastructure; D005456:Fluorescent Dyes / Q000737:chemistry; D006027:Glycosides / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D021962:Membrane Microdomains / Q000648:ultrastructure; D018613:Microscopy, Confocal; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D014312:Trisaccharides / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D000480:Alkynes; D001386:Azides; D003432:Cross-Linking Reagents; D005456:Fluorescent Dyes; D006027:Glycosides; D013438:Sulfhydryl Compounds; D014312:Trisaccharides; C008245:lactosides; D002784:Cholesterol