Synthesis of 3-aminopropyl β-glycoside of sialyl-3′-lactose and derived neoglycoconjugates as a tumor vaccine prototype and artificial antigens for the control of immune response

Abstract

Starting from the biotechnologically available trisaccharide sialyl 3´ lactose, representing the carbohydrate portion of the tumor associated ganglioside GM3, the corresponding 3 aminopropyl β glycoside (1) and 3 (4 maleimidobutanoylamino)propyl glycoside were syn thesized. The reaction of the latter with a thiolated derivative of the Megathura crenulata hemocyanine (KLH) afforded a carbohydrate-protein conjugate, a tumor vaccine prototype containing about 330 trisaccharide ligands attached to KLH. N Stearoylation of ligand 1 gave the model neoglycolipid for comparative study of the activity of mono and polyvalent immu nogens and the natural ganglioside GM3. A monovalent conjugate, in which ligand 1 is linked to biotin through an oligo(ethylene glycol) spacer and a polyvalent conjugate with a polyacryl amide carrier were also prepared. These conjugates are meant as covering antigens to assess the specificity and efficiency of the immune response in the ELISA assay.

Synthesis of a conjugate of 3´-sialyllactoside with recombinant flagellin as a carrier protein and assessment of its immunological activity in comparison with that of a similar hemocyanin-based conjugate

“…The target neoglycoconjugate 1 was obtained (Scheme 1) by reaction of thiol 3 27 with bromoacetylated flagellin 5.…”

Triterpenoid saponins from the roots ofAcanthophyllum gypsophiloidesRegel

“…To estimate the adjuvant properties of compounds 1 and 2 a series of test immunizations was carried out by using the synthetic vaccine neoglycoconjugate α-NeuAc-(2 → 3)-β-Gal p -(1 → 4)-β-Glc p -KLH (3’SL-KLH) on the basis of 3’-sialyllactoside (3’SL) ligands and keyhole limpet hemocyanin (KLH) protein carrier [ 26 ]. Four groups of mice were immunized with 40 µg of 3’SL-KLH together with 50 µg of compound 1 or 2 , or saponin from Quillaja bark, or without an adjuvant, and the specific anti-3’SL IgM and IgG responses were evaluated.…”

Synthesis of 2-aminoethyl 3′-(N-glycolylneuraminyl)-β-actoside and neoglycoconjugates based thereon — a prototype of a cancer vaccine and artificial antigens for the control of immune response

“…Dimethylformamide was distilled in an oil pump vacuum from phthalic anhydride and then from CaH 2 . 1 . The signals were assigned using homo and heteronuclear two dimensional COSY, TOCSY, and HSQC correlation spectra.…”

“…In our previous communication, 1 we described and studied the synthetic conjugate of spacered 3´ (N acetylneuraminyl) lactose, a carbohydrate chain of abundant tumor associ ated ganglioside GM3, with keyhole limpet Megathura crenulata hemocyanin (KLH), a natural highly immuno genic protein capable of initiating T cell immune re sponse. In our previous communication, 1 we described and studied the synthetic conjugate of spacered 3´ (N acetylneuraminyl) lactose, a carbohydrate chain of abundant tumor associ ated ganglioside GM3, with keyhole limpet Megathura crenulata hemocyanin (KLH), a natural highly immuno genic protein capable of initiating T cell immune re sponse.…”

“…D glucopyranoside(10). The organic layer was concentrated and chromatographed on a column (toluene-acetone, 3 : 2) to give 187 mg (91%) of diol 10 as a white foam, [α] D -21 (c 1, CHCl 3 ) 1. The mixture was concentrated and traces of pyridine and Aс 2 O were removed by co evaporation with toluene.…”