Chemical Synthesis of Δ-4,5 Unsaturated Heparan Sulfate Oligosaccharides for Biomarker Discovery

Apoorva Joshi; Pradeep Chopra; Andre Venot; Geert-Jan Boons

doi:10.1021/acs.orglett.4c00596

Chemical Synthesis of Δ-4,5 Unsaturated Heparan Sulfate Oligosaccharides for Biomarker Discovery

Apoorva Joshi, Pradeep Chopra, Andre Venot, Geert-Jan Boons^*

^*Corresponding author for this work

University of Georgia

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

A methodology is described that can provide heparan sulfate oligosaccharides having a Δ4,5-double bond, which are needed as analytical standards and biomarkers for mucopolysaccharidoses. It is based on chemical oligosaccharide synthesis followed by modification of the C-4 hydroxyl of the terminal uronic acid moiety as methanesulfonate. This leaving group is stable under conditions used to remove temporary protecting groups, O-sulfation, and hydrogenolysis. Treatment with NaOH results in elimination of the methanesulfonate and formation of a Δ4,5-double bond.

Original language	English
Pages (from-to)	2462-2466
Number of pages	5
Journal	Organic Letters
Volume	26
Issue number	12
DOIs	https://doi.org/10.1021/acs.orglett.4c00596
Publication status	Published - 29 Mar 2024

Bibliographical note

Publisher Copyright:
© 2024 The Authors. Published by American Chemical Society

Funding

This research was supported by the National Institutes of Health (P41GM103390 and HLBI R01HL151617 to G.J.B).

Funders	Funder number
National Institutes of Health	P41GM103390, HLBI R01HL151617
National Institutes of Health

Keywords

Carbohydrate Sequence
Heparitin Sulfate
Mesylates
Oligosaccharides/chemistry
Uronic Acids

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Cite this

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abstract = "A methodology is described that can provide heparan sulfate oligosaccharides having a Δ4,5-double bond, which are needed as analytical standards and biomarkers for mucopolysaccharidoses. It is based on chemical oligosaccharide synthesis followed by modification of the C-4 hydroxyl of the terminal uronic acid moiety as methanesulfonate. This leaving group is stable under conditions used to remove temporary protecting groups, O-sulfation, and hydrogenolysis. Treatment with NaOH results in elimination of the methanesulfonate and formation of a Δ4,5-double bond. ",

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AU - Boons, Geert-Jan

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AB - A methodology is described that can provide heparan sulfate oligosaccharides having a Δ4,5-double bond, which are needed as analytical standards and biomarkers for mucopolysaccharidoses. It is based on chemical oligosaccharide synthesis followed by modification of the C-4 hydroxyl of the terminal uronic acid moiety as methanesulfonate. This leaving group is stable under conditions used to remove temporary protecting groups, O-sulfation, and hydrogenolysis. Treatment with NaOH results in elimination of the methanesulfonate and formation of a Δ4,5-double bond.

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KW - Mesylates

KW - Oligosaccharides/chemistry

KW - Uronic Acids

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Chemical Synthesis of Δ-4,5 Unsaturated Heparan Sulfate Oligosaccharides for Biomarker Discovery

Abstract

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