Heparin sensing: Blue-chip binding
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Sasisekharan_Heparin sensing.pdf
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Author(s)
Shriver, Zachary H.
Sasisekharan, Ram
Date Issued
July 2013
Journal
Nature Chemistry
Publisher
Nature Publishing Group
Citation
Shriver, Zachary, and Ram Sasisekharan. “Heparin Sensing: Blue-Chip Binding.” Nature Chemistry 5, no. 8 (July 7, 2013): 644–646.
Version
Author's final manuscript
Abstract
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).
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. School of Engineering
Koch Institute for Integrative Cancer Research at MIT
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DOI of Published Version
https://doi.org/10.1038/nchem.1701
