ABSTRACT
Virus Replication ................................................................................... 821
16.3.3.3 Structure Affinity Relationship .............................................................. 822
16.3.3.4 Mimetics of Neu5Ac2en as Neuraminidase
Inhibitors ................................................................................................ 823
16.3.3.5 Summary and Outlook ........................................................................... 828
16.4 Selectin Antagonists ........................................................................................................... 828
16.4.1 Biological Rationale .............................................................................................. 828
16.4.2 Structure Affinity Relationship.............................................................................. 831
16.4.2.1 Selectin Structure ................................................................................... 832
16.4.2.2 Solution and Bioactive Conformation of sLe
...................................... 833
16.4.3 Families of Antagonists Identified So Far............................................................. 833
16.4.3.1 Mimetics of sLe
.................................................................................... 834
16.4.3.2 Modifications of sLe
............................................................................. 838
16.4.3.2.1 GlcNAc-Moiety ................................................................... 838
16.4.3.2.2 Gal-b(1-4)-GlcNAc Moiety................................................. 839
16.4.3.2.3 Glycopeptides ...................................................................... 839
16.4.3.3 Peptidic Antagonists .............................................................................. 840
16.4.4 Biological Evaluation ............................................................................................ 843
16.4.5 Summary and Outlook........................................................................................... 844
Acknowledgments ........................................................................................................................ 845
References..................................................................................................................................... 845
Over the past two decades, research has uncovered numerous biological roles for carbohydrates,
ranging from functions as simple as energy storage to complex processes that regulate transport,
protein function, intercellular adhesion, signal transduction, malignant transformation, and viral
and bacterial cell-surface recognition [1]. As carbohydrate-related drug-discovery targets are
increasingly discovered and validated, the tremendous pharmaceutical potential of carbohydrates is
beginning to be exploited by the pharmaceutical industry. In this review, we can only cover a
fraction of the potential drug-discovery applications; we focus on type 2 diabetes, viral infections
and inflammatory diseases. In addition, we review carbohydrate-based antagonists of the myelin-
associated glycoprotein (MAG), which show promising effects in axon regeneration. Numerous
other applications in the areas of thrombosis [2], bacterial infections [3] and anticancer vaccines [4]
are not covered here because they have recently been reviewed. Because of their stereochemical
diversity, carbohydrates are valuable tools for drug discovery, and they have been used as chiral
scaffolds in combinatorial chemistry. Applications of this kind have recently been reviewed [5]; it is
thus unnecessary to discuss these aspects in this chapter.
