Substructural specificity and polyvalent carbohydrate recognition by the Entamoeba histolytica and rat hepatic N-acetylgalactosamine/galactose lectins

David Yi, Reiko T. Lee, Patti Longo, Erich T. Boger, Yuan C. Lee, William A. Petri, Ronald L. Schnaar

Research output: Contribution to journalArticlepeer-review

Abstract

Both the Entamoeba histolytica lectin, a virulence factor for the causative agent of amebiasis, and the mammalian hepatic lectin bind to N-acetylgalactosamine (GalNAc) and galactose (Gal) nonreducing termini on oligosaccharides, with preference for GalNAc. Polyvalent GalNAc-derivatized neoglycoproteins have > 1000-fold enhanced binding affinity for both lectins. Substructural specificity studies revealed that the 3-OH and 4-OH groups of GalNAc were required for binding to both lectins, whereas only the E.histolytica lectin required the 6-OH group. Whereas GalNAc binds with 4-fold lower affinity to the E.histolytica lectin than to the mammalian hepatic lectin, galactosamine and N-benzoyl galactosamine bind with higher affinity to the E.histolytica lectin. Therefore, a synthetic scheme for converting polyamine carriers to poly-N-acyl galactosamine derivatives (linked through the galactosamine primary amino group) was developed to test whether such ligands would bind the E.histolytica lectin with high specificity and high affinity. Contrary to expectations, polyvalent derivatives including GalN6lys5, GalN4desmosine, GalN4Starburst® dendrimer, and GalN8Starburst® dendrimer demonstrated highly enhanced binding to the mammalian hepatic lectin but little or no enhancement of binding to the E.histolytica lectin. We propose that the mammalian hepatic lectin binds with greatest affinity to GalNAc 'miniclusters,' which mimic branched termini of N-linked oligosaccharides, whereas the E.histolytica lectin binds most effectively to 'maxiclusters,' which may mimic more widely spaced GalNAc residues on intestinal mucins.

Original languageEnglish (US)
Pages (from-to)1037-1043
Number of pages7
JournalGlycobiology
Volume8
Issue number10
DOIs
StatePublished - Oct 1998

Keywords

  • Cluster glycosides
  • Deoxysugars
  • Multivalent
  • Neoglycoconjugates
  • Rat hepatic lectin

ASJC Scopus subject areas

  • Biochemistry

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