The Chemistry and Biology of Heparan Sulfate'program project consists of several supporting Cores. This document describes the 'Shared Resources Core'. Project Leaders of the four projects (I - IV), i.e., Balagurunathan, Desai, Rajarathnam and Cooper, will be the local coordinators of the Shared Resources Core. Dr. Desai will oversee the availability of the Core to researchers from within the PEG as well as outside the PEG. At an appropriate point after the start of the PEG, most probably at the end of the first year, senior researchers (i.e., IVIosier, Liang, Victor, Vy Tran, Rajagopalan, and Ezzelerab) will be asked to assume the coordinatorships of the local sub-cores of the Shared Resource Core. The transfer of local coordinatorship to the six senior researchers will not absolve Dr. Desai of his responsibility of overseeing the availability of these resources to the wider glycoscience community. The Shared Resources Core will consists of five sub-cores including glycan synthesis, computational, glycan analysis, biophysics and chemokine sub-cores. These sub-cores will make available a number of resources to the members of the PEG and to the wider glycoscience community. These resources include synthetic tools including a) a panel of HS structures with differential sulfation pattern for study of HS-protein interactions and biological evaluation;b) a library of univalent 'Click'Xylosides for induced GAG biosynthesis;c) a library of multi-valent 'Click'Xylosides for induced GAG biosynthesis;d) a library of rare 3- O-sulfated disaccharide structures, e) a library of rare 3-O-sulfated disaccharides with ^S containing sulfate group;and f) ^'^^S labeled PAPS for studying HS biosynthesis;computational tools including g) a virtual library of GAG sequences;h) programs for optimized construction of sequences from library of disaccharide structures;i) software for automated docking and scoring of all library sequences;j) an algorithm for filtering sequences from the library;and k) methods for analysis of final results;analytical tools including mass spectrometry, capillary electrophoresis, and advanced chromatographic analysis;biophysical tools including stopped-flow fluorimetry, atomic force microscopy, thromboelastography, hemostasis analysis system, nuclear magnetic resonance, and isothermal calorimetry;and chemokine tools including interleukin-8, neutrophil activating peptide-2 and mouse KC proteins and variants.
The Shared Resources Core will support the 'The Chemistry and Biology of Heparan Sulfate'program project on all aspects of availability of resources. The PEG proposes design of heparan sulfate molecules that are potentially useful in the treatment of thrombotic and inflammatory disorders as well as resolve coagulation problems observed in during pig to non-human primate xenotransplantation.
|Ezzelarab, Mohamed B; Ekser, Burcin; Azimzadeh, Agnes et al. (2015) Systemic inflammation in xenograft recipients precedes activation of coagulation. Xenotransplantation 22:32-47|
|Sepuru, Krishna Mohan; Poluri, Krishna Mohan; Rajarathnam, Krishna (2014) Solution structure of CXCL5--a novel chemokine and adipokine implicated in inflammation and obesity. PLoS One 9:e93228|
|Mehta, Akul Y; Thakkar, Jay N; Mohammed, Bassem M et al. (2014) Targeting the GPIb? binding site of thrombin to simultaneously induce dual anticoagulant and antiplatelet effects. J Med Chem 57:3030-9|
|Bane Jr, Charles E; Gailani, David (2014) Factor XI as a target for antithrombotic therapy. Drug Discov Today 19:1454-8|
|Kalita, Mausam; Balivada, Sivasai; Swarup, Vimal Paritosh et al. (2014) A nanosensor for ultrasensitive detection of oversulfated chondroitin sulfate contaminant in heparin. J Am Chem Soc 136:554-7|
|Rajarathnam, Krishna; Rosgen, Jorg (2014) Isothermal titration calorimetry of membrane proteins - progress and challenges. Biochim Biophys Acta 1838:69-77|
|Tran, Vy M; Kuberan, Balagurunathan (2014) Synthesis of fluorophore-tagged xylosides that prime glycosaminoglycan chains. Bioconjug Chem 25:262-8|
|Safo, Martin K; Musayev, Faik N; Mosier, Philip D et al. (2014) Crystal structures of influenza A virus matrix protein M1: variations on a theme. PLoS One 9:e109510|
|Al-Horani, Rami A; Desai, Umesh R (2014) Designing allosteric inhibitors of factor XIa. Lessons from the interactions of sulfated pentagalloylglucopyranosides. J Med Chem 57:4805-18|
|Al-Horani, Rami A; Desai, Umesh R (2014) Recent advances on plasmin inhibitors for the treatment of fibrinolysis-related disorders. Med Res Rev 34:1168-216|
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