Current Organic Chemistry

ISSN: 1385-2728

Current Organic Chemistry
Volume 12, Number 4, March 2008

Contents

Bioorganic Chemistry
Guest Editor: Harri Lönnberg


Editorial Pp. 262


Chemical Strategies for Oligonucleotide-Conjugates Synthesis Pp. 263-290
Y. Singh, N. Spinelli and E. Defrancq
[Abstract]


Synthesis, Properties and Application of Nucleic Acids Containing Phosphorothiolate Linkages Pp. 291-308
James W. Gaynor and Richard Cosstick
[Abstract]


Reactions of Transglycosylation in the Nucleoside Chemistry Pp. 309-325
Jerzy Boryski
[Abstract]


Secondary Metabolites from Cyanobacteria: Complex Structures and Powerful Bioactivities Pp. 326- 341
Karl Gademann and Cyril Portmann
[Abstract]




Abstracts

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Editorial

The current issue is Part I of the annual thematic issue of Bioorganic Chemistry. Four extensive review articles are included, which offer a nice example of the width of this field. Transformation reactions of nucleosides, structural chemistry of secondary metabolites, synthesis of potentially chemotherapeutic oligonucleotides and methods for construction of conjugates of biopolymers are discussed. While these articles are of considerable general interest, they at the same time constitute a compilation of literature useful both for specialists working in these fields. The first contribution, written by Prof Defrancq and his co-workers, deals with synthesis of oligonucleotide conjugates. Such conjugates have received increasing interest in chemotherapy, in in vitro diagnostics and in in vivo imaging. This review offers an up-to-date survey of the methods exploited in tethering a variety of conjugate groups, ranging from peptides and sugars to fluorescent dyes and nanoparticles, to oligonucleotides. In addition, alternative approaches for immobilization of oligonucleotides to microarrays are described. The second review by Gaynor and Cosstick is a summary of the studies that have led to successful solid-phase synthesis of oligonucleotides having either the 3´- or 5´-bridging oxygen of the internucleosidic phosphodiester linkages replaced with sulfur. The effect of these modifications on the physico-chemical properties of nucleic acids, such as structure and chemical and enzymatic stability, has been summarized and the exploitation of the 3´-S-linkages in mechanistic studies of catalytic nucleic acids discussed. The third paper is a comprehensive review of the transglycosylation reactions of nucleosides by Prof Boryski. These reactions are of great importance, since structurally modified nucleosides are increasingly studied as potential antivirals and as consituents of therapeutic oligonucleotides. As far as sugar-modified nucleosides are concerned, exchange of the base moiety offers a shortcut for the preparation of all four modified nucleosides. Finally, Gademann and Portmann present an overview of the natural products from cyanobacteria, highlighting several classes of secondary metabolites. Some of these metabolites show promise in cancer therapy, some are extremely efficient chelators of iron and some are inhibitors of proteases. In other words, cyanobacteria secondary metabolites constitute a versatile source both for leads of drugs. I thank all the authors for their thorough work and hope that many organic chemists enjoy reading this issue.


Harri Lönnberg
Department of Chemistry
University of Turku
FIN-20014 Turku
Finland


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Chemical Strategies for Oligonucleotide-Conjugates Synthesis
Y. Singh, N. Spinelli and E. Defrancq

Oligonucleotide conjugates have found numerous applications in the field of diagnostics and therapeutics. Structurally diverse oligonucleotide conjugates have been prepared and evaluated for various applications. Research efforts have focused on the development of synthetic procedures to accomplish efficient oligonucleotide conjugation with different target molecules. Both on-support and solution-phase coupling procedures have been used to conjugate oligonucleotides. This review gives an account of major synthetic approaches available to prepare covalent oligonucleotide conjugates with diverse target molecules.


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Synthesis, Properties and Application of Nucleic Acids Containing Phosphorothiolate Linkages
James W. Gaynor and Richard Cosstick

A largely historical survey is presented on the development of methods for the synthesis of oligonucleotides containing either 3′-S- or 5′-S-phosphorothiolate linkages. The properties of these modifications are discussed with emphasis on their specific cleavage and the use of a metal ion specificity switch for investigating the role of metal ions in enzyme-catalysed DNA/RNA cleavage processes. Finally, the effect of the 3′-S-phosphorothiolate modification on the structure of nucleic acids is described.


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Reactions of Transglycosylation in the Nucleoside Chemistry
Jerzy Boryski

Mechanisms of transglycosylation reactions in the nucleoside chemistry and their modern interpretations are presented. Special attention is paid to the formation of kinetically controlled and thermodynamic products, reaction intermediates, correlation of tautomerism and regioselectivity in glycosyl migration reactions, their stereoselectivity and reversibility as well as side-reactions like anomerization or cyclization. Some synthetic applications of transglycosylation are also discussed.


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Secondary Metabolites from Cyanobacteria: Complex Structures and Powerful Bioactivities
Karl Gademann and Cyril Portmann

This review presents natural products from cyanobacteria. Several classes of secondary metabolites are highlighted. Toxic metabolites from these prokaryotic photosynthetic organisms include compounds such as microcystin, anatoxin and saxitoxin, which display hepatotoxicity and neurotoxicity. Their potential as drugs in cancer therapy is discussed based on the cryptophycin class of potent cytotoxic agents. The next part of this review highlights iron chelators from cyanobacteria, including schizokinen, synechobactin and anachelin. The biogenesis of anachelin is investigated as its mechanism of iron acquisition. Several indole alkaloids are then reviewed, from simple carbolines such as bauerines and nostocarboline to complex polycyclic structures such as hapalindole, welwitindolinone and ambiguine. The latter compounds present fascinating structure combined with powerful bioactivities and interesting biogenetic pathways. In the last part, protease inhibitors from cyanobacteria are discussed (cyanopeptolins, micropeptin and oscillapeptin) and their structure/activity relationships and selectivity for trypsin / chymotrypsin are presented. All these examples highlight the large structural variety of cyanobacterial metabolites combined with powerful biological activities. Cyanobacteria can thus be considered a prime source both for novel bioactive compounds and for leads for drugs.