Controlled sulfation of mixed-linkage glucan by Response Surface Methodology for the development of biologically applicable polysaccharides

Abstract

Endogenous and exogenous sulfated polysaccharides exhibit potent biological activities, including inhibiting blood coagulation and protein interactions. Controlled chemical sulfation of alternative polysaccharides holds promise to overcome limited availability and heterogeneity of naturally sulfated polysaccharides. Here, we established reaction parameters for the controlled sulfation of the abundant cereal polysaccharide, mixed-linkage β(1,3)/β(1,4)-glucan (MLG), using Box-Behnken Design of Experiments (BBD) and Response Surface Methodology (RSM). The optimization of the degree-of-substitution (DS) was externally validated through the production of sulfated MLGs (S-MLGs) with observed DS and M_w values deviating less than 20% and 30% from the targeted values, respectively. Simultaneous optimization of DS and M_w resulted in the same range of deviation from the targeted value. S-MLGs with DS > 1 demonstrated a modest anticoagulation effect versus heparin, and a greater P-selectin affinity than fucoidan. As such, this work provides a route to medically important polymers from an economical agricultural polysaccharide.

Keywords: Anticoagulant; Box-Behnken Design (BBD); Design of Experiments (DoE); Fucoidan; Mixed-linkage beta-glucan; P-selectin; Response Surface Methodology; Sulfated polysaccharide.