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Expedient Synthesis of Core Disaccharide Building Blocks from Natural Polysaccharides for Heparan Sulfate Oligosaccharide Assembly

Pawar, Nitin J. and Wang, Lei and Higo, Takuya and Bhattacharya, Chandrabali and Kancharla, Pavan K. and Zhang, Fuming and Baryal, Kedar and Huo, Chang-Xin and Liu, Jian and Linhardt, Robert J. and Huang, Xuefei and Hsieh-Wilson, Linda C. (2019) Expedient Synthesis of Core Disaccharide Building Blocks from Natural Polysaccharides for Heparan Sulfate Oligosaccharide Assembly. Angewandte Chemie International Edition, 58 (51). pp. 18577-18583. ISSN 1433-7851. PMCID PMC6901730. https://resolver.caltech.edu/CaltechAUTHORS:20190925-123342834

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Abstract

The complex sulfation motifs of heparan sulfate glycosaminoglycans (HS GAGs) play critical roles in many important biological processes. However, an understanding of their specific functions has been hampered by an inability to synthesize large numbers of diverse, yet defined, HS structures. Here, we describe a new approach to access the four core disaccharides required for HS/heparin oligosaccharide assembly from natural polysaccharides. The use of disaccharides as minimal precursors rather than monosaccharides greatly accelerates the synthesis of HS GAGs, providing key disaccharide and tetrasaccharide intermediates in about half the number of steps compared to traditional strategies. Rapid access to such versatile intermediates will enable the generation of comprehensive libraries of sulfated oligosaccharides for unlocking the ‘sulfation code’ and understanding the roles of specific GAG structures in physiology and disease.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1002/anie.201908805DOIArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/pmc6901730/PubMed CentralArticle
ORCID:
AuthorORCID
Pawar, Nitin J.0000-0002-9755-0652
Liu, Jian0000-0001-8552-1400
Hsieh-Wilson, Linda C.0000-0001-5661-1714
Additional Information:© 2019 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim. Manuscript received: July 15, 2019; Revised manuscript received: August 22, 2019; Accepted manuscript online: September 25, 2019; Version of record online: November 6, 2019. Financial support was provided by the NIH Common Fund grant U01 GM116262-03 and the NIH R01 grant HL62244. We thank Dr. Mona Shahgholi in the CCE Division Mass Spectrometry Facility and Dr. David Vander Velde in the CCE Division NMR Facility at Caltech. The authors declare no conflict of interest.
Funders:
Funding AgencyGrant Number
NIHU01 GM116262-03
NIHHL62244
Subject Keywords:carbohydrates; heparan sulfate; glycosaminoglycans; Oligosaccharides; Synthesis design
Issue or Number:51
PubMed Central ID:PMC6901730
Record Number:CaltechAUTHORS:20190925-123342834
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20190925-123342834
Official Citation:N. J. Pawar, L. Wang, T. Higo, C. Bhattacharya, P. K. Kancharla, F. Zhang, K. Baryal, C.-X. Huo, J. Liu, R. J. Linhardt, X. Huang, L. C. Hsieh-Wilson, Angew. Chem. Int. Ed. 2019, 58, 18577; doi: https://doi.org/10.1002/anie.201908805
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:98857
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:25 Sep 2019 21:13
Last Modified:10 Apr 2020 21:27

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