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Tunable Heparan Sulfate Mimetics for Modulating Chemokine Activity

Sheng, Gloria J. and Oh, Young In and Chang, Shuh-Kuen and Hsieh-Wilson, Linda C. (2013) Tunable Heparan Sulfate Mimetics for Modulating Chemokine Activity. Journal of the American Chemical Society, 135 (30). pp. 10898-10901. ISSN 0002-7863. PMCID PMC3732023. https://resolver.caltech.edu/CaltechAUTHORS:20131024-101709748

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Abstract

Heparan sulfate (HS) glycosaminoglycans participate in critical biological processes by modulating the activity of a diverse set of protein binding partners. Such proteins include all known members of the chemokine superfamily, which are thought to guide the migration of immune cells through their interactions with HS. Here, we describe an expedient, divergent synthesis to prepare defined HS glycomimetics that recapitulate the overall structure and activity of HS glycosaminoglycans. Our approach uses a core disaccharide precursor to produce a variety of differentially sulfated glycopolymers. We demonstrate that a specific trisulfated mimetic antagonizes the chemotactic activity of the proinflammatory chemokine RANTES with potency similar to that of heparin, without inhibiting serine proteases in the blood coagulation cascade. Our work provides a general strategy for modulating chemokine activity and dissecting the pleiotropic functions of HS/heparin through the presentation of defined sulfation motifs within polymeric scaffolds.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1021/ja4027727DOIArticle
http://pubs.acs.org/doi/abs/10.1021/ja4027727PublisherArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3732023/PubMed CentralArticle
ORCID:
AuthorORCID
Hsieh-Wilson, Linda C.0000-0001-5661-1714
Additional Information:© 2013 American Chemical Society. ACS AuthorChoice. Received: March 19, 2013; Published: July 23, 2013. We thank Rochelle Diamond at the Flow Cytometry Cell Sorting Facility, Dr. Mona Shahgholi in the Mass Spectrometry Facility, and Dr. David VanderVelde at the High Resolution NMR Facility at Caltech. We also thank Dr. Osamu Yoshie (Kinki University, School of Medicine, Japan) for generously providing murine L1.2 cells stably expressing CCR3 and CCR5. This work was supported by the NIH (R01 GM093627).
Funders:
Funding AgencyGrant Number
NIHR01 GM093627
Issue or Number:30
PubMed Central ID:PMC3732023
Record Number:CaltechAUTHORS:20131024-101709748
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20131024-101709748
Official Citation:Tunable Heparan Sulfate Mimetics for Modulating Chemokine Activity Gloria J. Sheng, Young In Oh, Shuh-Kuen Chang, and Linda C. Hsieh-Wilson Journal of the American Chemical Society 2013 135 (30), 10898-10901
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:42042
Collection:CaltechAUTHORS
Deposited By: Jason Perez
Deposited On:24 Oct 2013 21:31
Last Modified:03 Oct 2019 05:54

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