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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Main Authors: Shriver, Zachary H., Sasisekharan, Ram
Other Authors: Massachusetts Institute of Technology. Department of Biological Engineering
Format: Article
Language:en_US
Published: Nature Publishing Group 2014
Online Access:http://hdl.handle.net/1721.1/88988
https://orcid.org/0000-0001-9344-0205
https://orcid.org/0000-0002-2085-7840
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author Shriver, Zachary H.
Sasisekharan, Ram
author2 Massachusetts Institute of Technology. Department of Biological Engineering
author_facet Massachusetts Institute of Technology. Department of Biological Engineering
Shriver, Zachary H.
Sasisekharan, Ram
author_sort Shriver, Zachary H.
collection MIT
description 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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spelling mit-1721.1/889882022-09-26T10:33:12Z Heparin sensing: Blue-chip binding Shriver, Zachary H. Sasisekharan, Ram Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. School of Engineering Koch Institute for Integrative Cancer Research at MIT Shriver, Zachary H. Sasisekharan, Ram 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) 2014-08-22T16:41:19Z 2014-08-22T16:41:19Z 2013-07 Article http://purl.org/eprint/type/JournalArticle 1755-4330 1755-4349 http://hdl.handle.net/1721.1/88988 Shriver, Zachary, and Ram Sasisekharan. “Heparin Sensing: Blue-Chip Binding.” Nature Chemistry 5, no. 8 (July 7, 2013): 644–646. https://orcid.org/0000-0001-9344-0205 https://orcid.org/0000-0002-2085-7840 en_US http://dx.doi.org/10.1038/nchem.1701 Nature Chemistry Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Nature Publishing Group PMC
spellingShingle Shriver, Zachary H.
Sasisekharan, Ram
Heparin sensing: Blue-chip binding
title Heparin sensing: Blue-chip binding
title_full Heparin sensing: Blue-chip binding
title_fullStr Heparin sensing: Blue-chip binding
title_full_unstemmed Heparin sensing: Blue-chip binding
title_short Heparin sensing: Blue-chip binding
title_sort heparin sensing blue chip binding
url http://hdl.handle.net/1721.1/88988
https://orcid.org/0000-0001-9344-0205
https://orcid.org/0000-0002-2085-7840
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