Synthesis and Evaluation of 1,5-Dithia-D-Iaminaribiose, Triose, and Tetraose as Truncated β-(1→ 3)-Glucan Mimetics

The preparation and characterization of a series of di-, tri-, and tetrasaccharide analogues of beta-(1 -> 3)-glucans is described in which each pyranoside ring is replaced by a 5-thiopyranosyl ring and each glycosidic oxygen by a thioether. These oligomeric 1,5-dithio-n-glucopyranose derivatives were shown to inhibit the staining of human neutrophils and of mouse macrophages by fluorescent anti-CR3 and anti-Dectin-1 antibodies, respectively. The compounds were also demonstrated to stimulate phagocytosis and pinocytosis indicative of binding to the carbohydrate binding domains of complement receptor 3 (CR3) and Dectin-1. Activity in all three assays was optimum at the level of the trisaccharide mimic, suggesting that, while the replacement of ethereal oxygens by thio ethers results in a greater affinity for the aromatic lined hydrophobic binding pockets, the presence of multiple longer C-S bonds eventually results in a mismatch and a loss of affinity.