VII Summary and Conclusions
Heparin and heparan sulfate are complex glycosaminoglycans that play multiple roles in the normal physiology and pathophysiology of the human body. The structural diversity displayed by these GAG chains makes them extremely challenging molecules to analyze. Also unlike DNA and proteins, it is not possible to amplify these structures, as their biosynthesis is not template driven. Therefore in cases where sample amounts are limited (e.g., isolated cell surface HS), it further magnifies the problem. Methodology for structural characterization of these molecules has primarily focused on: (1) chemical or enzymatic techniques for specifically degrading them to smaller oligosaccharides; (2) efficient means to separate them, coupled with sensitive detection procedures; and (3) the use of NMR and mass spectrometry. Together these techniques have provided a wealth of information for analyzing these complex mixtures as well as in determining sequences of isolated pure oligosaccharides. As analytical techniques get more sophisticated and are adapted to study sugar structure (e.g., MS/MS), they open more avenues to get structural insights into these complex mixtures. Having the PEN framework adds another layer of sophistication to the analysis of these mixtures as it enables the possible decoding of the structural information by taking into account multiple experimental data sets as constraints for sequence refinement.
Heparin and heparan sulfate have been implicated as playing crucial roles in many disease states by interacting with important proteins at key steps in different pathways. To better understand these interactions it is essential to know the key structural elements from both the sugar side as well as the protein side. While advances in protein technology have enabled a greater understanding from the protein side, understanding of complex sugar structure is lagging behind. Therefore, an understanding of the structure and sequence information displayed by the sugars that facilitate these interactions would possibly provide new targets for therapeutic intervention in different disease states. As the field of "glycomics" gains more importance, advances in analytical capabilities represent the cornerstone that will help shape the future.
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Chemistry and Biology of Heparin and Heparan Sulfate H.G. Garg, RJ. Linhardt and C.A. Hales (Editors) © 2005 Elsevier Ltd. All rights reserved
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