A Hexasaccharide Containing Rare 2‐ O ‐Sulfate‐Glucuronic Acid Residues Selectively Activates Heparin Cofactor II
Abstract: Glycosaminoglycan (GAG) sequences that selectively target heparin cofactor II (HCII), a key serpin present in human plasma, remain unknown. Using a computational strategy on a library of 46 656 heparan sulfate hexasaccharides we identified a rare sequence consisting of consecutive glucuronic acid 2‐O‐sulfate residues as selectively targeting HCII. This and four other unique hexasaccharides were chemically synthesized. The designed sequence was found to activate HCII ca. 250‐fold, while leaving aside antithrombin, a closely related serpin, essentially unactivated. This group of rare designed hexasaccharides will help understand HCII function. More importantly, our results show for the first time that rigorous use of computational techniques can lead to discovery of unique GAG sequences that can selectively target GAG‐binding protein (s), which may lead to chemical biology or drug discovery tools.
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Erschienen in
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A Hexasaccharide Containing Rare 2‐ O ‐Sulfate‐Glucuronic Acid Residues Selectively Activates Heparin Cofactor II ; volume:56 ; number:9 ; year:2017 ; pages:2312-2317 ; extent:6
Angewandte Chemie / International edition. International edition ; 56, Heft 9 (2017), 2312-2317 (gesamt 6)
- Urheber
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Sankaranarayanan, Nehru Viji
Strebel, Tamara R.
Boothello, Rio S.
Sheerin, Kevin
Raghuraman, Arjun
Sallas, Florence
Mosier, Philip D.
Watermeyer, Nicholas D.
Oscarson, Stefan
Desai, Umesh R.
- DOI
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10.1002/anie.201609541
- URN
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urn:nbn:de:101:1-2022092706121959745752
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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15.08.2025, 07:26 MESZ
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Beteiligte
- Sankaranarayanan, Nehru Viji
- Strebel, Tamara R.
- Boothello, Rio S.
- Sheerin, Kevin
- Raghuraman, Arjun
- Sallas, Florence
- Mosier, Philip D.
- Watermeyer, Nicholas D.
- Oscarson, Stefan
- Desai, Umesh R.
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Development of a peptide that selectively activates protein phosphatase-1 in living cells
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