Abstract

Carbosilane dendrimers periphery-functionalized with lactotriaose (GlcNAcβ1–3Galβ1–4Glc) with valencies of three, four, six, and twelve were prepared for use in a lectin-binding assay. A lactotriaose derivative was prepared from d-glucosamine and d-lactose derivatives. The N-Troc-protected glucosamine glycosyl donor and 3′-O-unprotected lactose glycosyl acceptor were condensed in the presence of silver trifluoromethanesulfonate and methylsulfenyl bromide to provide corresponding trisaccharide with new β-1-3 linkages in 92% yield. The protection group of the trisaccharide was transformed into an acetyl group. The 4-pentenyl glycoside was prepared from the acetate via glycosyl bromide. The alkene was converted into acetyl sulfide by addition of thioacetic acid under radical conditions. The lactotriaose unit was linked with carbosilane dendrimers to afford acetyl-protected glycodendrimers. De-O-acetylation of the dendrimers was carried out in the presence of sodium methoxide and then aq NaOH to give the desired lactotriaose clusters using a carbosilane dendrimer backbone. Their biological activities toward WGA were evaluated by fluorescence methods. The binding constants of free lactotriaose and trivalent, tetravalent, hexavalent, and dodecavalent glycodendrimers to WGA were determined to be 1.1 × 10³, 4.4 × 10⁴, 5.1 × 10⁴, 2.8 × 10⁶, and 1.3 × 10⁶ M⁻¹, respectively. The hexavalent glycodendrimer showed a 2500-fold larger binding effect than that of free lactotriaose.

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Keywords: WGA; Glycocluster; Carbosilane dendrimer; Lactotriaose

Article Outline

1. Introduction

2. Results and discussion

2.1. Syntheses of glycodendrimers

2.2. Interaction of glycodendrimers with WGA

3. Conclusion

4. Experimental

4.1. General methods

4.1.1. Benzyl O-[3,4,6,-tri-O-acetyl-2-deoxy-2-(2,2,2,-trichloroethoxycarbonylamino)- β-d-glucopyranosyl]-(1 → 3)-O-(2,6-di-O-benzyl-4-O-acetyl-β-d-galactopyranosyl)-(1 → 4)-2,3,6-tri-O-benzyl-β-d-glucopyranoside (4)

4.1.1.1. Prepared from 1 and 2

4.1.1.2. Prepared from 1 and 3

4.1.2. Benzyl O-(2-acetoamido-3,4,6,-tri-O-acetyl-2-deoxy-β-d-glucopyranosyl)-(1 → 3)-O-(2,6-di-O-benzyl-4-O-acetyl-β-d-galactopyranosyl)-(1 → 4)-2,3,6-tri-O-benzyl-β-d-glucopyranoside (5)

4.1.3. O-(2-Acetoamido-3,4,6,-tri-O-acetyl-2-deoxy-β-d-glucopyranosyl)-(1 → 3)-O-(2,4,6-tri-O-acetyl-β-d-galactopyranosyl)-(1 → 4)-2,3,6-tri-O-acetyl-β-d-glucopyranosyl acetate (6)

4.1.4. O-(2-Acetamido-2-deoxy-β-d-glucopyranosyl)-(1 → 3)-O-(β-d-galactopyranosyl)-(1 → 4)-d-glucopyranose (7)

4.1.5. 4-Pentenyl (2-acetoamido-3,4,6,-tri-O-acetyl-2-deoxy-β-d-glucopyranosyl)-(1 → 3)-O-(2,4,6-tri-O-acetyl-β-d-galactopyranosyl)-(1 → 4)-2,3,6-tri-O-acetyl-β-d-glucopyranoside (8)

4.1.6. 5-Acetylthiopentyl (2-acetoamido-3,4,6,-tri-O-acetyl-2-deoxy-β-d-glucopyranosyl)-(1 → 3)-O-(2,4,6-tri-O-acetyl-β-d-galactopyranosyl)-(1 → 4)-2,3,6-tri-O-acetyl-β-d-glucopyranoside (9)

4.1.7. Acetylated trivalent glycodendrimer (14)

4.1.8. Acetylated tetravalent glycodendrimer (15)

4.1.9. Acetylated hexavalent glycodendrimer (16)

4.1.10. Acetylated dodecavalent glycodendrimer (17)

4.1.11. Trivalent glycodendrimer (18)

4.1.12. Tetravalent glycodendrimer (19)

4.1.13. Hexavalent glycodendrimer (20)

4.1.14. Dodecavalent glycodendrimer (21)

4.2. Fluorescence measurements

Acknowledgements

References