Show simple item record

dc.contributor.authorLane, R.S.
dc.contributor.authorSt. Ange, K.
dc.contributor.authorZolghadr, B.
dc.contributor.authorLiu, X.
dc.contributor.authorSchäffer, C.
dc.contributor.authorLinhardt, Robert J.
dc.contributor.authorDeAngelis, P.L.
dc.date2017
dc.date.accessioned2022-06-27T16:01:10Z
dc.date.available2022-06-27T16:01:10Z
dc.date.issued2017-07-01
dc.identifier.citationExpanding Glycosaminoglycan Chemical Space: Towards the Creation of Sulfated Analogs, and Novel and Chimeric Polymers, R. S. Lane, K. St. Ange, B. Zolghadr, X. Liu, C. Schäffer, R. J. Linhardt, P. L. DeAngelis, Glycobiology, 27, 646–656, 2017.
dc.identifier.issn14602423
dc.identifier.issn9596658
dc.identifier.urihttps://doi.org/10.1093/glycob/cwx021
dc.identifier.urihttps://hdl.handle.net/20.500.13015/5624
dc.descriptionGlycobiology, 27, 646–656
dc.descriptionNote : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
dc.description.abstractGlycosaminoglycans (GAGs) have therapeutic potential in areas ranging from angiogenesis, inflammation, hemostasis and cancer. GAG bioactivity is conferred by intrinsic structural features, such as disaccharide composition, glycosidic linkages and sulfation pattern. Unfortunately, the in vitro enzymatic synthesis of defined GAGs is quite restricted by a limited understanding of current GAG synthases and modifying enzymes. Our work provides insights into GAG-active enzymes through the creation of sulfated oligosaccharides, a new polysaccharide and chimeric polymers. We show that a C6-sulfonated uridine diphospho (UDP)-glucose (Glc) derivative, sulfoquinovose, can be used as an uronic acid donor, but not as a hexosamine donor, to cap hyaluronan (HA) chains by the HA synthase from the microbe Pasteurella multocida. However, the two heparosan (HEP) synthases from the same species, PmHS1 and PmHS2, could not employ the UDP-sulfoquinovose under similar conditions. Serendipitously, we found that PmHS2 co-polymerized Glc with glucuronic acid (GlcA), creating a novel HEP-like polymer we named hepbiuronic acid [-4-GlcAβ1-4-Glcα1-]n. In addition, we created chimeric block polymers composed of both HA and HEP segments; in these reactions GlcA-, but not N-acetylglucosamine-(GlcNAc), terminated GAG acceptors were recognized by their noncognate synthase for further extension, likely due to the common β-linkage connecting GlcA to GlcNAc in both of these GAGs. Overall, these GAG constructs provide new tools for studying biology and offer potential for future sugar-based therapeutics.
dc.description.sponsorshipNational Institutes of Health
dc.languageen_US
dc.language.isoENG
dc.relation.ispartofThe Linhardt Research Labs Online Collection
dc.relation.ispartofRensselaer Polytechnic Institute, Troy, NY
dc.relation.ispartofGlycobiology
dc.relation.urihttps://harc.rpi.edu/
dc.subjectBiology
dc.subjectChemistry and chemical biology
dc.subjectChemical and biological engineering
dc.subjectBiomedical engineering
dc.titleExpanding Glycosaminoglycan Chemical Space: Towards the Creation of Sulfated Analogs, and Novel and Chimeric Polymers
dc.typeArticle
dcterms.isPartOfJournal
dcterms.isVersionOfhttps://doi.org/10.1093/glycob/cwx021
dc.rights.holderIn Copyright : this Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). https://rightsstatements.org/page/InC/1.0/
dc.creator.identifierhttps://orcid.org/0000-0003-2219-5833
dc.relation.departmentThe Linhardt Research Labs.
dc.relation.departmentThe Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
rpi.description.pages646-656
rpi.description.volume27


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record