Biomedical Technology Resources
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Resource for Integrated Glycotechnology

Kelley W. Moremen, Ph.D.
P41RR005351
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Center Overview

The central goal of the Research Resource for Integrated Glycotechnology is to increase understanding of the molecular basis of protein-carbohydrate interactions in disease and to develop more powerful technologies necessary to achieve this understanding. The carbohydrates (glycans) found on cell surfaces and circulating as parts of soluble glycoproteins play a role in many biomedically important processes, including inflammatory response, hormone action, malignancy, viral and bacterial infections and cell differentiation. Over the past few years the Resource has given particular attention to glycosaminoglycans, the polymeric materials of mammalian extracellular matrices and their circulating counterparts that include heparin, heparan sulfate, and chondroitin sulfate. These materials exhibit extraordinary diversity because of their differential sulfation patterns. Analysis and synthesis of particular isoforms in addition to the investigation of their protein interactions and consequent biological effects is particularly challenging. The Resource combines a number of complimentary technologies to tackle these challenges: synthetic chemistry, nuclear magnetic resonance (NMR), mass spectrometry (MS), computational biology, protein expression, and cell-based assays. As new technologies are developed, applications are pursued through collaborative and service projects, and the technologies are disseminated through an extensive training program.

Impact on Human Health

The importance of therapeutic glycosaminoglycans, such as heparin in the prevention of clot formation in circulatory disease or dialysis procedures, is widely recognized. However, closely related heparan sulfate, chondroitin sulfate and other glycosaminoglycan structures also play important roles in the regulation of growth factors and signaling events occurring during development. All can be degraded in disease and provide diagnostic serum markers. Chondroitin sulfate, for example, is a major structural component of cartilage and is often degraded in arthritis and joint disease. A number of congenital diseases are also linked to deficiencies in the synthesis and disposition of glycosaminoglycans.