Conjugation of oligosaccharides by reductive amination to amine modified chondroitin oligomer and gamma-cyclodextrin.
Carbohydrates present on cell surfaces participate in numerous biological recognition phenomena including cell-cell interactions, cancer metastasis and pathogen invasion. Therefore, synthetic carbohydrates have a potential to act as pharmaceutical substances for treatment of various pathological phenomena by inhibiting specifically the interaction between cell surface carbohydrates and their protein receptors (lectins). However, the inherently low affinity of carbohydrate-protein interactions has often been an obstacle for successful generation of carbohydrate based pharmaceuticals. Multivalent glycoconjugates, i.e. structures carrying several copies of the active carbohydrate sequence in a carrier molecule, have been constructed to overcome this problem. Here we present two novel types of multivalent carbohydrate conjugates based on chondroitin oligomer and cyclodextrin carriers. These carriers were modified to express primary amino groups, and oligosaccharides were then bound to carrier molecules by reductive amination. Multivalent conjugates were produced using the human milk type oligosaccharides LNDFH I (Lewis-b hexasaccharide), LNnT, and GlcNAcbeta1-3Galbeta1-4GlcNAcbeta1-3Galbeta1-4Glc.
Weikkolainen
Krista
K
Department of Biological and Environmental Sciences, University of Helsinki, P. O. Box 56, 00014, Helsinki, Finland.
Aitio
Olli
O
Blomqvist
Maria
M
Natunen
Jari
J
Helin
Jari
J
D000588:Amines / Q000138:chemical synthesis / Q000737:chemistry; D002240:Carbohydrate Sequence; D002807:Chondroitin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D003959:Diamines / Q000737:chemistry; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry; D006001:Glycoconjugates / Q000096:biosynthesis / Q000138:chemical synthesis* / Q000737:chemistry*; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D009844:Oligosaccharides / Q000096:biosynthesis / Q000138:chemical synthesis* / Q000737:chemistry*; D010084:Oxidation-Reduction; D012799:Sialyltransferases / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D047408:gamma-Cyclodextrins / Q000138:chemical synthesis / Q000737:chemistry*; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
D000588:Amines; D003959:Diamines; D004337:Drug Carriers; D006001:Glycoconjugates; D009844:Oligosaccharides; D047408:gamma-Cyclodextrins; D002807:Chondroitin; C009475:trimethylenediamine; D012799:Sialyltransferases; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase