The arsenal of synthetic methodology of carbohydrates has increased significantly in recent decades and coincides with the discovery and characterization of biologically active polysaccharides. Glycosaminoglycans showcase the intertwining of biology and chemistry, both of which are required to completely understand protein-GAG interactions that are essential to biological systems. Small GAG oligomers and analogs are useful probes of the specific biological interactions responsible for activity and the various strategies utilized in the synthesis of GAGs represent state-of-the-art synthetic methodology. Early synthetic efforts employed Koenigs-Knorr-type

Figure 11 The nonglycosaminoglycan analogs of heparin sulfate.

glycosylations that were often low yielding with moderate a,0-selectivities. Although halo sugars are still widely used today, new glycosylation strategies have been developed that achieve consistently high yields and selectivities. The strategy most widely utilized in GAG synthesis is Schmidt's trichloroacetimidate methodology. The high efficiency and substrate generality of the method allow for the use of uronic acid building blocks. The design and installation of the hexosamine unit has also benefited from recent advances in synthetic methodology. The 2-deoxy-2-amino functionality was normally derived from glucosamine or galactose amine; however, azidonitration and sulfonamidation of glycals are particularly suited for GAG synthesis.

The chemical synthesis of GAG oligomers, their derivatives, and analogs is an important tool in determining their biological roles. High degree of functionalization coupled with diversity among individual GAG members continue to make them challenging synthetic targets. As with heparin, the chemical preparations of GAGs play a critical role in probing and elucidating specific protein-GAG interactions. Chemical syntheses of heparin clearly established the anionic carboxylate and sulfate groups as the sites of protein interaction. The application of this methodology to other GAGs is forthcoming, but it is clear that only synthesis allows for the specific modifications needed to reveal the sites responsible for biological activity.

Good Carb Diet

Good Carb Diet

WHAT IT IS A three-phase plan that has been likened to the low-carbohydrate Atkins program because during the first two weeks, South Beach eliminates most carbs, including bread, pasta, potatoes, fruit and most dairy products. In PHASE 2, healthy carbs, including most fruits, whole grains and dairy products are gradually reintroduced, but processed carbs such as bagels, cookies, cornflakes, regular pasta and rice cakes remain on the list of foods to avoid or eat rarely.

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