A Hexasaccharide Containing Rare 2‐ O ‐Sulfate‐Glucuronic Acid Residues Selectively Activates Heparin Cofactor II

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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.

Location: Deutsche Nationalbibliothek Frankfurt am Main

Extent: Online-Ressource

Language: Englisch

Bibliographic citation: 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)

Creator: 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: 10.1002/anie.201609541

URN: urn:nbn:de:101:1-2022092706121959745752

Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.

Last update: 15.08.2025, 7:26 AM CEST

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Associated

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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A Hexasaccharide Containing Rare 2‐ O ‐Sulfate‐Glucuronic Acid Residues Selectively Activates Heparin Cofactor II

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A Hexasaccharide Containing Rare 2‐ O ‐Sulfate‐Glucuronic Acid Residues Selectively Activates Heparin Cofactor II

A Hexasaccharide Containing Rare 2‐ O ‐Sulfate‐Glucuronic Acid Residues Selectively Activates Heparin Cofactor II

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Heparin Cofactor During Early Stage of Coagulation in Vitro and During Bleeding in Vivo

Zacopride selectively activates the Kir2.1 channel via a PKA signaling pathway in rat cardiomyocytes

Zacopride selectively activates the Kir2.1 channel via a PKA signaling pathway in rat cardiomyocytes

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Oxidation of methionine residues activates the high-threshold heat-sensitive ion channel TRPV2

TC-G 1008 facilitates epileptogenesis by acting selectively at the GPR39 receptor but non-selectively activates CREB in the hippocampus of pentylenetetrazole-kindled mice

TC-G 1008 facilitates epileptogenesis by acting selectively at the GPR39 receptor but non-selectively activates CREB in the hippocampus of pentylenetetrazole-kindled mice

Catalyst-free late-stage functionalization to assemble α-acyloxyenamide electrophiles for selectively profiling conserved lysine residues

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ADAM 17 selectively activates the IL ‐6 trans‐signaling/ERK MAPK axis in KRAS ‐addicted lung cancer

ADAM 17 selectively activates the IL ‐6 trans‐signaling/ERK MAPK axis in KRAS ‐addicted lung cancer

Basic Residues of β-Sheet A Contribute to Heparin Binding and Activation of Vaspin (Serpin A12)

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Schriftgut

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The complete N-terminal extension of heparin cofactor II is required for maximal effectiveness as a thrombin exosite 1 ligand

The complete N-terminal extension of heparin cofactor II is required for maximal effectiveness as a thrombin exosite 1 ligand

A Hexasaccharide Containing Rare 2‐ O ‐Sulfate‐Glucuronic Acid Residues Selectively Activates Heparin Cofactor II

A Hexasaccharide Containing Rare 2‐ O ‐Sulfate‐Glucuronic Acid Residues Selectively Activates Heparin Cofactor II

Determination of Antithrombin, Heparin Co-Factor and Heparin in Plasma Using the Chromogenic Substrate S2238

Determination of Antithrombin, Heparin Co-Factor and Heparin in Plasma Using the Chromogenic Substrate S2238

Development of a peptide that selectively activates protein phosphatase-1 in living cells

Development of a peptide that selectively activates protein phosphatase-1 in living cells

Heparin Cofactor During Early Stage of Coagulation in Vitro and During Bleeding in Vivo

Heparin Cofactor During Early Stage of Coagulation in Vitro and During Bleeding in Vivo

Zacopride selectively activates the Kir2.1 channel via a PKA signaling pathway in rat cardiomyocytes

Zacopride selectively activates the Kir2.1 channel via a PKA signaling pathway in rat cardiomyocytes

Oxidation of methionine residues activates the high-threshold heat-sensitive ion channel TRPV2

Oxidation of methionine residues activates the high-threshold heat-sensitive ion channel TRPV2

TC-G 1008 facilitates epileptogenesis by acting selectively at the GPR39 receptor but non-selectively activates CREB in the hippocampus of pentylenetetrazole-kindled mice

TC-G 1008 facilitates epileptogenesis by acting selectively at the GPR39 receptor but non-selectively activates CREB in the hippocampus of pentylenetetrazole-kindled mice

Catalyst-free late-stage functionalization to assemble α-acyloxyenamide electrophiles for selectively profiling conserved lysine residues

Catalyst-free late-stage functionalization to assemble α-acyloxyenamide electrophiles for selectively profiling conserved lysine residues

ADAM 17 selectively activates the IL ‐6 trans‐signaling/ERK MAPK axis in KRAS ‐addicted lung cancer

ADAM 17 selectively activates the IL ‐6 trans‐signaling/ERK MAPK axis in KRAS ‐addicted lung cancer

Basic Residues of β-Sheet A Contribute to Heparin Binding and Activation of Vaspin (Serpin A12)

Basic Residues of β-Sheet A Contribute to Heparin Binding and Activation of Vaspin (Serpin A12)

Schriftgut

Heparin

The complete N-terminal extension of heparin cofactor II is required for maximal effectiveness as a thrombin exosite 1 ligand

The complete N-terminal extension of heparin cofactor II is required for maximal effectiveness as a thrombin exosite 1 ligand

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