Effects of sulfate group in red seaweed polysaccharides on anticoagulant activity and cytotoxicity

•We prepared kinds of red seaweed polysaccharide derivatives by chemical modification.•A comprehensive exploration combining various influencing factors together was investigated.•The substitution position is the most important influencing factor on bioactivity of red seaweed glycans.•The anticoagulant effect of the substitution positions follows the sequence: A-2, G-2>G-4>G-6.•The cytotoxic effect of the substitution positions follows the sequence: G-6>G-4>G-2>A-2. In this paper, the structural effects of two main red seaweed polysaccharides (agarose and carrageenan) and their sulfated derivatives on the anticoagulant activity and cytotoxicity were investigated. The substitution position rather than the substitution degree of sulfate groups shows the biggest impact on both the anticoagulant activity and the cell proliferation. Among them, C-2 of 3,6-anhydro-α-d-Galp is the most favorable position for substitution, whereas C-6 of β-d-Galp is the most disadvantageous. Moreover, the secondary structures of glycans also play a key role in biological activities. These demonstrations warrant that the red seaweed polysaccharides should be seriously considered in biomedical applications after carefully tailoring the sulfate groups.