Sulfated Alkyl Glucopyranans with Potent Antiviral Activity Synthesized by Ring-Opening Copolymerization of Anhydroglucose and Alkyl Anhydroglucose Monomers

Shiming Bai,Takashi Yoshida,Hideki Nakashima,Shuqin Han,Taisei Kanamoto,Davaanyam Budragchaa

doi:10.1155/2015/317420

Abstract

Sulfated glucopyranans having long alkyl groups were prepared by the ring-opening copolymerization of benzylated 1,6-anhydroglucopyranose with 3-O-octadecyl 1,6-anhydro-β-d-glucopyranose monomers, and subsequent deprotection and sulfation. Water-soluble sulfated glucopyranans with 2.8 and 4.7 mol% of 3-O-octadecyl group and lower molecular weights ofM-n= 2.5 × 103–5.1 × 103have potent anti-HIV activity at 0.05–1.25 μg/mL, even though sulfated polysaccharides with molecular weights belowM-n= 6 × 103had low anti-HIV activity. The interaction with poly-l-lysine as a model compound of proteins was analyzed by SPR, DSL, and zeta potential, indicating that the sulfated 3-O-octadecyl glucopyranans had high association and low dissociation rate constants, and the particle size increased after addition of poly-l-lysine. The anti-HIV activity was induced by electrostatic interaction between sulfate groups and amino groups of poly-l-lysine and by the synergistic effect of the hydrophobic long alkyl chain and hydrophilic sulfated group.

Highlights

We have continuously investigated the ring-opening polymerization of anhydrosugar derivatives, which is a superior method to prepare stereoregular polysaccharides with high molecular weights and defined structures [1, 2] and elucidation of the relationship between the structure and biological activity of polysaccharides [3, 4]
Curdlan sulfate, which was synthesized by sulfation of naturally occurring curdlan with a linear (1 → 3)-β-dglucopyranoside structure [7], was found to have potent antiHIV activity in the infection of MT-4 cells with HIV at completely inhibitory concentrations as low as 3.3 μg/mL and the activity depended on the molecular weights and degree of sulfation [6]
We report the synthesis of sulfated alkyl polysaccharides by the ring-opening copolymerization of LGTBE with 2,4-di-O-benzyl 3-O-octadecyl-1,6-anhydro-βd-glucopyranose (LGDBE3-18) and subsequent debenzylation to recover hydroxyl groups without elimination of the 3-O-octadecyl group

Summary

Introduction

We have continuously investigated the ring-opening polymerization of anhydrosugar derivatives, which is a superior method to prepare stereoregular polysaccharides with high molecular weights and defined structures [1, 2] and elucidation of the relationship between the structure and biological activity of polysaccharides [3, 4]. It is important to obtain polysaccharides with desired molecular weights and defined structures for the investigation of the structure-biological activity relationship, because there are many naturally occurring polysaccharides that have specific biological activities; in general, they have very complex structures and it is difficult to know the relationship. We introduced a long alkyl chain into curdlan sulfates with high anti-HIV activity by the ionic interaction of sulfate groups and quaternary ammonium salt of the long alkyl chain. A membrane filter was coated with the alkyl curdlan sulfates due to the hydrophobic interaction of the long alkyl chains with the surface of the membrane

Objectives

Methods

Results

Conclusion