Iterative synthesis of spacered glycodendrons as oligomannoside mimetics and evaluation of their antiadhesive properties.
Dendrimer chemistry is an attractive concept for mimicry of the highly branched character of the bioactive carbohydrates found as part of a cell's sugar coat, called the glycocalyx. Glycodendrimers have thus been used to study biological processes occurring on cell surfaces, such as bacterial adhesion. This paper details a new approach in glycodendrimer synthesis, in which a 3,6-diallylated carbohydrate is utilised as core molecule, hydroboration-oxidation is the activating step, and glycosylation with branched and unbranched sugar trichloroacetimidates is used for dendritic growth. To obtain pure dendritic pseudo-tri- and -heptasaccharides in good yields, radical addition of mercaptoethanol to peripheral double bonds was also evaluated with great success. A collection of six new hyperbranched glycodendrons was tested for their potential as inhibitors of type 1 fimbriae-mediated bacterial adhesion in an ELISA and the results were interpreted with regard to sugar valency and spacer characteristics.
Heidecke
Christoph D
CD
Otto Diels Institute of Organic Chemistry, Christiana Albertina University of Kiel, Otto-Hahn-Platz 4, 24098 Kiel, Germany.
Lindhorst
Thisbe K
TK
D001422:Bacterial Adhesion / Q000187:drug effects; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D050091:Dendrimers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli / Q000187:drug effects / Q000502:physiology; D006001:Glycoconjugates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006031:Glycosylation; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D050091:Dendrimers; D006001:Glycoconjugates; D009844:Oligosaccharides; C028569:oligomannoside