Heparin sensing: Blue-chip binding

Heparin is an anionic polysaccharide that has tremendous clinical importance as an anticoagulant. Several dyes have been developed that can detect heparin, and the latest example — named Mallard Blue — has now been shown to have excellent sensing properties under biologically relevant conditions. Heparin and heparan sulfate (HS) are complex linear polysaccharides that modulate a range of normal and disease-related biological functions. The basic disaccharide repeat unit of each consists of a glucosamine linked to a uronic acid1, 2. Modification of these biosynthesized polymers — primarily by O- and N-sulfonation — leads to structural heterogeneity within the chains. Heparin can be viewed as a 'specialized' version of HS, composed primarily of highly sulfated chains, with ~60–80% of the disaccharide units consisting of 2-O sulfo iduronic acid and 6-O sulfo, N-sulfo glucosamine. In a typical heparin chain, repeats of this trisulfated disaccharide unit are interrupted by other minor sequences — including a 3-O-sulfate-containing pentasaccharide sequence that binds to the small protein antithrombin and, as a consequence, is responsible for heparin's anticoagulant activity3, 4. Conversely, HS composition can vary more significantly, although there do seem to be six major disaccharide constituents5 (Fig. 1a).National Institutes of Health (U.S.) (R37 GM057073-13