Synthesis of Per-Glycosylated β-Cyclodextrins Having Enhanced Lectin Binding Affinity

• Published in: Journal of organic chemistry Vol. 64; no. 2; pp. 522 - 531
• Main Authors: García-López, Juan José, Hernández-Mateo, Fernando, Isac-García, Joaquín, Kim, Jin Mi, Roy, René, Santoyo-González, Francisco, Vargas-Berenguel, Antonio
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 22.01.1999; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; Physical Sciences; Science & Technology; CONCANAVALIN-A; RECOGNITION; LIGANDS; CALIXSUGARS; CHEMISTRY; DENDRIMERS; OLIGOSACCHARIDE-BRANCHED CYCLODEXTRINS; DRUG-TARGETING VECTORS; CLUSTER; DERIVATIVES
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo981576y

A cyclomaltooligosaccharide containing seven α-(1→4)-d-glucopyranosyl units (β-cyclodextrins) was transformed into heptakis 6-deoxy-6-iodo (13) and heptakis 6-amino-6-deoxy (25) derivatives using known procedures. Compound 13 was peracetylated and condensed in one pot with the known peracetylated pseudothiouronium salts of β-d-glucopyranose (4), β-d-galactopyranose (5), or β-d-N-acetylglucopyranosylsamine (6) or with α-d-1-deoxy-1-thiomannopyranose (8) using cesium carbonate in dimethylformamide. Alternatively, peracetylated 4-aminophenyl-α-d-mannopyranoside (9) was transformed into either extended pseudothiouronium 11 following N-chloroacetylation and nucleophilic substitution by thiourea or into 4-isothiocyanatophenyl α-d-mannopyranoside 12 using thiophosgene. Each of the four thiolated sugar derivatives 4 − 6 or 8 were also coupled to heptakis chloroacetamido β-CD 26 obtained from heptakis amine 25 after N-chloroacetylation. Further incorporation of a hexamethylenediamine spacer arm onto heptakis iodo β-CD 13 using thiol derived from mono-Boc derivative 36 and coupling to isothiocyanate 12 after suitable deprotection afforded permannosylated derivative 38. Zemplén de-O-acetylation of all β-CD derivatives provided water-soluble persubstituted compounds containing d-glucopyranosides (18, 30), d-galactopyranosides (19, 31), d-N-acetylglucosaminides (20, 32), and d-mannopyranosides (22, 24, 34, 39), respectively. The compounds were then evaluated for their relative binding properties toward natural carbohydrate binding plant lectins using both microtiter plate competitive inhibition experiments, double sandwich assays using horseradish peroxidase labeled lectins and by turbidimetric assays. The plant lectins from Pisum sativum (pea), Arachis hypogea (peanut), Canavalia ensiformis (Concanavalin A), and Triticum vulgaris (WGA, wheat germ agglutinin) were used for β-d-glucose, β-d-galactose, α-d-mannose, and β-d-N-acetylglucosamine, respectively. All persubstituted β-CDs showed good to excellent inhibitory properties together with abilities to cross-link their analogous plant lectins. The capacity of perglycosylated β-CDs to anchor both microtiter plate-coated lectins and their corresponding peroxidase-labeled derivatives further confirmed the usefulness of these multivalent neoglycoconjugates in bioanalytical assays.