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....
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| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2014
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| Online Access: | http://hdl.handle.net/1721.1/88988 https://orcid.org/0000-0001-9344-0205 https://orcid.org/0000-0002-2085-7840 |
| Summary: | 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). |
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