The University of North Carolina at Chapel Hill

The State University of New York

Rensselaer Polytechnic Institute

Massachusetts Institute of Technology

The United States of America, As Represented by the Secretary, Department of Health and Human Services

University of Illinois

Duke University

Nutech Ventures

Musc Foundation for Research Development

Jian Liu

Yongmei Xu

Rafal Pawlinski

Robert J Linhardt

Jinghua Chen

Ding Xu

Jine Li

Robert D Rosenberg

Daniel R Knapp

John J Schwartz

Anders Malmström

Deepak Shukla

Vaibhav Tiwari

Bryan P Toole

Nicholas W Shworak

Fikri Avci

Lijuan Zhang

Michael B Duncan

Linda M S Fritze

Erica Sparkenbaugh

Stavros Garantziotis

Ava M Munoz

Guowei Su

Katelyn Arnold

John W Hollingsworth

Zhangjie Wang

Po-Hung Hsieh

Edward Harris

Guoqing Xia

Provided herein are small molecule compounds, including non-anticoagulant heparan sulfate oligosaccharide molecules, having anti-inflammatory properties and capable of interacting with high mobility group box 1 (HMGB1) proteins in a manner sufficient to affect an interaction between the HMGB1 protein and a receptor for advanced glycation end products (RAGE). Also provided herein are methods of treating Paracetamol (APAP) overdose in subjects.

Sulfated oligosaccharides having anti-inflammatory activity

Methods of synthesizing chondroitin sulfate oligosaccharides are provided. Enzymatic schematic approaches to synthesizing structurally defined homogenous chondroitin sulfate oligosaccharides at high yields are provided. Synthetic chondroitin sulfate oligosaccharides ranging from 3-mers to 15-mers are provided.

Enzymatic synthesis of homogeneous chondroitin sulfate oligosaccharides

Heparin compounds and synthetic heparin analogues having short acting anticoagulant activity are provided. Methods of synthesizing such heparin compounds, including chemoenzymatic pathways using sulfotransferase enzymes are provided. Methods of treating subjects in need of anticoagulant activity are provided.

Short-acting heparin-based anticoagulant compounds and methods

Chondroitin sulfate compounds comprising chondroitin sulfate backbone 19 mer, CS-A 19 mer, CS-C 19 mer, CS-E 19 mer, C8 backbone 13 mer, C8-A 13 mer, CS-C 13 mer, CS-E 13 mer and/or combinations thereof are provided. Methods of treating histone toxicity in a subject are provided, the methods including administering to a subject a chondroitin sulfate compound to treat the histone toxicity in the subject. Pharmaceutical compositions for use in treating histone toxicity and/or sepsis are provided. Methods of treating sepsis in a subject are provided, the methods including administering to a subject a chondroitin sulfate compound to treat the sepsis in the subject.

Cell protective methods and compositions

Methods for preparing synthetic heparins are provided. Synthetic heparin compounds, including ultralow molecular weight heparin compounds are provided. Also provided are methods of chemoenzymatically synthesizing structurally homogeneous ultra-low molecular weight heparins. Heparin compounds provided herein can have anticoagulant activity.

Chemoenzymatic synthesis of structurally homogeneous ultra-low molecular weight heparins

Methods and systems for synthesizing heparin compounds are provided. The chemoenzymatic synthesis of structurally homogeneous low molecular weight heparins that have a reversible anticoagulant activity is provided. Also disclosed are heparin compounds having anticoagulant activity, including a binding affinity to antithrombin and an anti-Xa activity, but no detectable anti-lla activity. Additionally, provided are synthetic, low-molecular weight heparin compounds with reversible anticoagulant activity, where the anticoagulant activity is reversible by protamine.

Reversible heparin molecules and methods of making and using the same

Described herein is the finding that hyaluronan antagonists that inhibit hyaluronan signaling are capable of inhibiting airway inflammation and airway hyperresponsiveness (AHR). The present disclosure provides a method of preventing or reducing AHR in a subject suffering from or at risk for AHR by administering a hyaluronan antagonist. Also provided is a method of treating an airway disease or disorder in a subject by administering a hyaluronan antagonist. Hyaluronan antagonists include, for example, heparosan and hyaluronan oligosaccharides (oHAs). In some embodiments, the hyaluronan antagonist is administered locally to the airway, such as with an inhaler or nebulizer.

Uses of antagonists of hyaluronan signaling

Heparin is synthesized from a polysaccharide comprised of a 1-4 glycosidically linked alternating polymer of uronic acid and glucosamine residues, wherein the uronic acid is selected from iduronic and glucuronic acid, wherein the glucosamine is partially N-sulfated; by a series of selective reactions catalyzed by recombinant enzymes.

Enzymatic synthesis of sulfated polysaccharides

3-OST-5 proteins, and nucleic acid molecules encoding the same. Recombinant host cells, recombinant nucleic acids and recombinant proteins are also disclosed, along with methods of producing each. Isolated and purified antibodies to 3-OST-5 homologs, and methods of producing the same, are also disclosed. 3OST-5 gene products have biological activity in specific heparan sulfate 3-O-sulfotransferase reactions. These reactions provide unique modified heparan sulfate. Thus, therapeutic methods involving this activity are also disclosed.

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A pointed carbon fiber electrospray ionization emitter has a length of electrically conductive fiber that is present within a lumen of a microfluidic device, and protrudes from the terminus. A point is present on an end of the electrically conductive fiber, or the electrically conductive fiber is otherwise sufficiently small on the end to create a desired spray. A conductor supplies electrical current to the electrically conductive fiber. Fluid to be sprayed is transported through the lumen and out of the terminus of the lumen, and an electrical field established by the conductive fiber distributes and sprays the fluid. The emitter is rugged and is able to generate stable electrospray over a wide range of flow rates, voltages, and surface tension variations.

Electrospray ionization using pointed fibers

Disclosed are novel isolated nucleic acids and substantially pure protein preparations for naturally occurring and synthetic or chimeric heparan sulfate D-glicosaminyl 3-O-sulfo-transferases (3-OSTs). Also disclosed are uses for these genes and proteins, including uses for the modification and sequencing of glycosaminoglycans.

Heparan sulfate D-glucosaminyl 3-O-sulfotransferases, and uses therefor

Growing community of inventors

Chapel Hill, NC, United States of America

Jian Liu