Kuberan Balagurunathan
Assistant Professor of Medicinal Chemistry
B.S. St. Joseph College's, India
Ph.D. University of Iowa
Kuby Balagurunathan's PubMed Literature Search
Research
In the post-genomics era, it is now accepted that complex glycoconjugates such as proteoglycan regulate numerous patho-physiological processes in all living species. They carry enormous structural information in terms of sulfation, epimerization, domain organization, chain length, number of chains and type of chains along with their core proteins. Production of proteoglycans with such high complexity occurs in template-independent fashion seamlessly, yet our understanding of their biosynthesis, structures and functions is somewhat incomplete and imperfect. We are developing a wide variety of chemical biology tools to define the biosynthetic pathways of heparan sulfate and related glycosaminoglycans (GAG) such as chondroitin sulfate and dermatan sulfate. We synthesize heparin and heparan sulfate structures with a dozen recombinant enzymes to define the structural basis for the interactions of growth factors and Heparan sulfates and the subsequent biological actions. We recently found that a library of click-xylosides produce distinct GAG chains in cellular systems and proposed a GAGOSOME model for the dynamic regulation of combinatorial GAG biosynthesis. These molecular tools are currently used in the lab to define the snap shots of biosynthetic events and signaling events that are associated with development and diseases with a final goal to advance the study of heparanomics..
GAGOSOME MODEL
References
1. Raman K, Kuberan B (2010) Chemical Tumor Biology of Heparan Sulfate Proteoglycans. Current Chemical Biology 4:20-31
2. Babu P, Kuberan B (2010) Fluorescent Tagged Heparan Sulfate Precursor Oligosaccharides to Probe the Enzymatic Action of Heparitinase I. Analytical Biochemistry 396:124-132
3. Sigulinsky C, Babu P, Victor XV, Kuberan B (2010) Preparation and Characterization of 15N-enriched, Size-Defined Heparan Sulfate Precursor Oligosaccharides. Carbohydrate Research 345:250-256
4. Victor XV, Nguyen TKN, Ethirajan M, Tran VM, Nguyen KV, Kuberan B (2009) Investigating the Elusive Mechanism of Glycosaminoglycan Biosynthesis. Journal of Biological Chemistry 284:25842-25853
5. Garud DR*, Tran VM*, Victor XV, Koketsu M, Kuberan B (2008) Inhibition of Heparan Sulfate and Chondroitin Sulfate Proteoglycan Biosynthesis. Journal of Biological Chemistry 283:28881-28887 [*authors contributed equally]
6 Kuberan B, Ethirajan M, Victor XV, Tran VM, Nguyen KV, Do A (2008) "Click"- Xylosides Initiate Glycosaminoglycan Biosynthesis in a Mammalian Cell line. ChemBioChem 9:198–200
7. Kuberan B, Lech M, Borjigin J, Rosenberg RD (2004) Light Induced 3-O-Sulfotransferase Expression Alters Pineal Heparan Sulfate Fine Structure: A Surprising Link to Circadian Rhythm. Journal of Biological Chemistry 279:(7)5053-5054
8. Lawrence R, Kuberan B, Lech M, Beeler DL, Rosenberg RD (2004) Mapping Critical Biological Motifs and Biosynthetic Pathways of Heparan Sulfate. Glycobiology 14:(5)467-479
9. Kuberan B, Beeler DL, Lawrence R, Lech M, Rosenberg RD (2003) Rapid Two Step Synthesis of Mitrin from Heparosan: A Replacement for Heparin. Journal of the American Chemical Society 125:(41)12424-12425
Updated 8/15/2010
