SUBSTRUCTURAL SPECIFICITY AND POLYVALENT CARBOHYDRATE-RECOGNITION BY THE ENTAMOEBA-HISTOLYTICA AND RAT HEPATIC N-ACETYLGALACTOSAMINE GALACTOSE LECTINS/

Both the Entamoeba histolytica lectin, a virulence factor for the caus ative agent of amebiasis, and the mammalian hepatic lectin bind to N-a cetylgalactosamine (GalNAc) and galactose (Gal) nonreducing termini on oligosaccharides, with preference for GalNAc, Polyvalent GalNAc-deriv atized neoglycoproteins have >1000-fold enhanced binding affinity for both lectins (Adler,P,, Wood,S,J,, Lee,Y,C,, Lee,R,T,, Petri,W.A.,Jr. and Schnaar,R,L,,1995, J, Biol, Chem,, 270, 5164-5171), substructural specificity studies revealed that the 3-OH and 4-OH groups of GalNAc w ere required for binding to both lectins, whereas only the E,histolyti ca lectin required the 6-OH group. Whereas GalNAc binds with 3-fold lo wer affinity to the E,histolytica lectin than to the mammalian hepatic lectin, galactosamine and N-benzoyl galactosamine bind with higher af finity 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, polyvale nt derivatives including GalN(6)lys(5), GalN(4)desmosine, GalN(4)Starb urst(TM) dendrimer, and GalN(8)Starburst(TM) dendrimer demonstrated hi ghly enhanced binding to the mammalian hepatic lectin but little or no enhancement of binding to the E,histolytica lectin, We propose that t he mammalian hepatic lectin binds with greatest affinity to GalNAc ''m iniclusters,'' which mimic branched termini of N-linked oligosaccharid es, whereas the E,histolytica lectin binds most effectively to ''maxic lusters,'' which may mimic more widely spaced GalNAc residues on intes tinal mucins.