Current Organic Chemistry

ISSN: 1385-2728

Current Organic Chemistry
Volume 11, Number 7, May 2007

Contents


Complex Carbohydrates
Guest Editors: Nasir-ud-Din and Daniel C. Hoessli


Editorial Pp. 577


Glycosphingolipid Structure and Function in Membranes Pp. 579-589
Annika Wedeking and Gerhild van Echten-Deckert
[Abstract]


Glycosyltransferase and Glypiation Inhibitors Pp. 591-607
Evelyne Walker-Nasir, Ishtiaq Ahmad, Muhammad Saleem and Daniel C. Hoessli
[Abstract]


Glycosylphosphatidylinositol (GPI) Anchored Proteins of Plasmodium falciparum: Antigenic Determinants and Role of Sugar Moieties in the GPI Anchor Pp. 609-618
Nasir-Ud-Din, Ishtiaq Ahmad, Daniel C. Hoessli, Evelyne Walker-Nasir and M. Iqbal Choudhary
[Abstract]


Functional and Structural Roles of GPI Moieties in Mammalian Plasma Membranes Pp. 619-626
Daniel C. Hoessli, Sebastien Tauzin, Nasir-ud-Din and Bettina Borisch
[Abstract]


Roles of Polysialic Acid-Neural Cell Adhesion Molecule (PSA-NCAM) in Synaptic Plasticity Pp. 627-635
Eduardo Gascon, Laszlo Vutskits and Jozsef Zoltan Kiss
[Abstract]


General Articles


Halogen Dance Reaction and its Application in Organic Synthesis Pp. 637-646
Marcus Vinícius Nora de Souza
[Abstract]


Synthesis, Photophysical and Photobiological Study of Synergic Photosensitizer: Zinc-Phthalocyanine with Ca²⁺ Chelating Agent Pp. 647-654
Claure N. Lunardi, Jeane C.G. Rotta and Antonio C. Tedesco
[Abstract]




Abstracts

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Editorial

The present issue of Current Organic Chemistry is devoted to complex glycoconjugates with special emphasis on those glyconjugates that contribute to the structural and functional properties of membranes.

Glycosphingolipids are reviewed by Wedeking and van Echten-Deckert for their structural contributions to membranes, especially from the point of view of the specific microdomain properties they impart to the outer leaflet.

The complexity of glycan structures obviously rests on an impressive toolkit of enzymes that allow the biosynthesis and remodeling of those molecules. Realizing the importance of naturally-occurring glycans in the biology of the cell, the review by Walker-Nasir et al. provides an up-to-date discussion of the inhibitors available to prevent the synthesis of glycans and their potential applications in therapeutics.

The two reviews by Nasir-ud-Din et al. and Hoessli et al. focus on the glycosylphosphatidylinositol glycolipid (GPI) that serves as membrane anchor for a host of parasite and mammalian cell-surface proteins. In the Nasir-ud-Din review, the structural and functional roles of the GPI anchor in the malaria parasite P. falciparum are considered, as GPI moieties condition both the biology of the parasite itself and the host-parasite relationship. In addition, the review discusses the possible involvement of galactose in the malarial anchor. Hoessli et al. then give an account of what has been achieved by studying and utilizing GPI anchors in mammalian cells. From the rather exotic study subject that it was some twenty years ago, systematic analysis of GPI anchor function and judicious use of its properties have considerably enriched our understanding of membrane dynamics.

Lastly, Kiss et al. illustrate how complex glycans such as polysialic acid (PSA) moieties added to neuronal surface proteins control the function of individual cells and the assembly and remodeling of neuronal circuits. The importance of PSA moieties in neuronal plasticity provides an eloquent example of how complex glycans are involved in patterning multicellular organizations.


Daniel C. Hoessli
Dept. of Pathology and Immunology
Faculty of Medicine, University of Geneva
Cenre Médical Universitaire 1,
rue Michel-Servet, 1211 Geneve 4, Switzerland


Nasir-ud-Din
Institute of Molecular Sciences
and Bioinformatics,
35/1 Nisbet Road,
Lahore, Pakistan


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Glycosphingolipid Structure and Function in Membranes
Annika Wedeking and Gerhild van Echten-Deckert

Glycosphingolipids (GSLs) are amphiphilic membrane components of all eukaryotic cells. They are located primarily in the plasma membrane and to a lesser extend in intracellular membranes of related organelles. Even some bacteria are known to synthesize GSLs or at least use GSLs generated by hosts. Gangliosides, a group of complex sialic acid-containing GSLs are particularly abundant in the central nervous system. Although gangliosides were long believed to be essential for neuronal function, a groundbreaking step towards understanding their physiological role was the generation of mice models deficient in distinct biosynthetic steps of these complex lipids. During the last 15 – 20 years also the role of their more simple metabolic intermediates like glucosylceramide, ceramide and sphingosine-1-phosphate came into the focus of interest.

The present review provides a brief survey of GSL metabolism and intracellular transport, as well as some recent developments regarding ganglioside function in membranes. From the huge amount of data concerning the involvement of gangliosides in various cellular processes, we focused on their role in neurodegeneration and cancer on the one hand and on their function as receptors for toxins or bacteria including the respective elicited signalling pathways on the other hand.


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Glycosyltransferase and Glypiation Inhibitors
Evelyne Walker-Nasir, Ishtiaq Ahmad, Muhammad Saleem and Daniel C. Hoessli

Understanding the chemistry and biology of protein glycosylation is a major challenge in proteomics and glycomics research. Due to their pivotal role in the biosynthesis of complex oligosaccharides and glycoconjugates, protein glycosylation enzymes are targets of choice for the development of inhibitors. Glycosyltransferase and glypiation (GPI anchoring) inhibitors that are of potential therapeutic value for the treatment of diseases associated with glycosylation defects are reviewed in the light of recent developments.


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Glycosylphosphatidylinositol (GPI) Anchored Proteins of Plasmodium falciparum: Antigenic Determinants and Role of Sugar Moieties in the GPI Anchor
Nasir-Ud-Din, Ishtiaq Ahmad, Daniel C. Hoessli, Evelyne Walker-Nasir and M. Iqbal Choudhary

GPI-anchored proteins are ubiquitously expressed on eukaryotic cell surfaces and are involved in a variety of vital functions ranging from adhesion to enzymatic catalysis. This review focuses on GPI-anchored proteins in malaria and the role of carbohydrate moieties in malarial proteins. Malaria remains a formidable threat to human beings even in the twenty-first century. Malaria vaccine development to prevent morbidity and mortality has generated comprehensive molecular information on many immunologically-relevant malarial antigens but an effective anti-malaria vaccine is still unavailable. Several malarial antigenic proteins have been considered as promising vaccine candidates. Merozoite surface protein 1 (MSP-1) and merozoite surface protein 2 (MSP-2) from the asexual stages of the malarial life cycle are prominent amongst malarial antigens. Modifications of MSPs are significantly important as the natural MSPs offer better protection against malaria compared to recombinant proteins that lack post-translational modifications. Development of viable vaccine(s) against malaria has met considerable difficulties and it is likely that the lack of post-translational modification may have been a contributory factor. The role of galactose residues in MSP-1 is reviewed in this article.


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Functional and Structural Roles of GPI Moieties in Mammalian Plasma Membranes
Daniel C. Hoessli, Sebastien Tauzin, Nasir-ud-Din and Bettina Borisch

Glycosylphosphatidylinositol (GPI) moieties consist of a hydrophobic core (two to three fatty acids attached to phosphatidylinositol) continued by a chain of five hexoses (the glycolinker) that is covalently linked via phosphoethanolamine to the C-terminal amino acid of a long list of mammalian proteins. This glycolipid moiety imparts characteristic membrane properties (diffusion, lateral mobility and clustering) to proteins and the glycolinker component constitutes a molecular motif recognized by lectins, cytokines and bacterial toxins. Due to the saturated acyl chains of its core lipids, GPIs preferentially insert in sphingolipid-rich domains of the plasma membrane outer leaflet, and the capacity of GPI-anchored proteins to participate in transmembrane signalling depends on this property. GPI-anchored proteins can be made to associate with membranes and thus offer a therapeutic potential in tumor vaccine preparation and complement protection. Research on the role of GPI-anchored proteins in membrane structure and function has fruitfully contributed to the elaboration of today’s prevailing concepts of membrane organization.


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Roles of Polysialic Acid-Neural Cell Adhesion Molecule (PSA-NCAM) in Synaptic Plasticity
Eduardo Gascon, Laszlo Vutskits and Jozsef Zoltan Kiss

Isoforms of the neuronal cell adhesion molecule (NCAM) carrying the linear homopolymer of alpha 2,8-linked sialic acid (polysialic acid, PSA) have emerged as particularly attractive candidates for promoting plasticity in the nervous system. The large negatively charged PSA chain of NCAM is considered as a spacer that reduces adhesion forces between cells allowing dynamic changes in membrane contacts. However, accumulating evidence also suggest that PSA-NCAM mediated interactions lead to activation of intracellular signaling cascades that are fundamental to the biological functions of the molecule. An important role of PSA-NCAM appears to be during development, when its expression level is high and where it contributes to regulate transformations of cell shape, cell growth or cell migration. However, PSA-NCAM does persist in adult brain structures that display a high degree of plasticity as the hippocampus where it is involved in activity-induced synaptic plasticity. In this review, we will discuss the recent findings on the structure, synthesis and signaling activity of PSA-NCAM essential to understand its role in synaptic plasticity.


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Halogen Dance Reaction and its Application in Organic Synthesis
Marcus Vinícius Nora de Souza

Halogen dance (HD) reaction is an important tool in modern organic chemistry. This reaction is defined as halogen migration induced by bases, normally in aromatic and heteroaromatic systems. It is successfully applied in aromatic and different classes of heteroaromatic compounds, such as thiophene, quinoline, pyridine, thiazole, and many others. Due to the importance of this reaction, the aim of this review is to discuss the HD reaction and its application in organic synthesis between 1992-2005.


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Synthesis, Photophysical and Photobiological Study of Synergic Photosensitizer: Zinc-Phthalocyanine with Ca²⁺ Chelating Agent
Claure N. Lunardi, Jeane C.G. Rotta and Antonio C. Tedesco

A novel phthalocyanine derivative containing a Ca²⁺ chelating agent with structure similar to EDTA has been synthesized in 3 steps. The addition of a chelating agent to the phthalocyanine macrocycle make it a synergic compound useful for PDT.