Current Organic Chemistry - Volume 13, Issue 11, 2009

This thematic issue of bioorganic chemistry is largely focused on chemistry of oligonucleotides. Four extensive reviews highlighting various aspects of oligonucleotide chemistry are included. While these articles provide specialists with useful compilations of recent literature, they at the same time should be of considerable general interest, owing to the increasing number of new biological roles discovered for nucleic acids, in particular for RNA, during the past decade. Novel methods for preparation, detection, conjugation and tailoring of nucleic acids are continuously needed to elucidate the multiple biological functions of nucleic acids in more detail and to realize the increased understanding as novel diagnostic and chemotherapeutic approaches. Prof Oretskaya with her co-workers describe how various 2'-functionalized oligonucleotides may be synthesized and how such structurally modified probes bearing a carboxy, carbaldehyde, amino or iodoacetyl group in this particular position may be exploited in studying the recognition of nucleic acids by protein enzymes. The group of Prof Asanuma has designed and synthesized functional oligonucleotides by making use of acyclic non-nucleosidic building blocks that do not retard hybridization and allow construction of photoresponsive and fluorescent probes. The results of these extensive studies are summarized in their review article. N-Alkylated nucleobases play a role in many biological phenomena, the well-known examples being the 5'-terminal cap in mRNA and snRNA and the DNA base modifications as an origin of mutagenesis and chemical carcinogenesis. In addition, alkylated bases are exploited as chemotherapeutics and fluorescent markers. The synthesis and chemical, physical, biological and spectroscopic and properties of N-alkylguanine derivatives, are summarized in an extensive review of Prof Kovacs and his co-workers. Finally, Prof Scrimin et al. critically evaluates the potential and limitations of various multivalent catalysts based on small molecule scaffolds, dendrimers and nanoparticles. The underlying theme is recognition of the prerequisites for cooperativite action of several catalytic functions. This discussion is largely focused on cleavage of phosphate esters, above all the internucleosidic phosphodiester linkages of nucleic acids. I thank all the authors for their thorough work and hope that many organic chemists enjoy reading this issue.

This review outlines the design and synthesis of oligonucleotides bearing 2'-modified residues at predetermined positions within the strand. The relative merits of incorporation of reactive carboxyl, carbonyl, iodoacetamide and disulfide-containing groups into oligonucleotides were considered along with solid-phase synthesis of DNA 2'- conjugates. The specific cross-linking of 2'-substituted oligonucleotides to nucleic acid-binding proteins (transcription factor NF-κB, restriction-modification enzymes) was shown to be helpful in scanning the protein-DNA interface and studying the conformational dynamics of biopolymer ensembles. The future perspectives of chemically reactive DNA constructs as specific protein decoys are discussed.

Multivalent systems are well known for their enhanced ability to bind multivalent counterparts. This contribution addresses the question whether they can also behave as cooperative catalysts. Analyzing examples mostly (but not only) from our own laboratory we show what conditions are required for obtaining cooperativity in catalysis. Systems considered range from simple, discrete catalysts to dendrimers and monolayer-protected gold nanoparticles. Reactions taken into considerations for our analysis are the hydrolyses of carboxylate- and phosphate esters.

The growing field of DNA technology requires new modified DNAs that can perform advanced functions. No matter how we optimize the length and sequence of DNA using only the four naturally occurring nucleotides, potential performance is limited. In this review, we describe a facile and effective method of rationally designing new functional DNA by focusing on acyclic scaffolds, especially threoninols, which are utilized to incorporate functional molecules into DNA. Wedge-type insertion of a functional molecule with a planar structure of proper size in D-threoninol to DNA does not destabilize the duplex, although the backbone structure is changed. Rather, intercalation offsets such distortions and significantly raises the melting temperature of the DNA duplex. Based on the wedge-type insertion, photoresponsive DNA (tethering azobenzenes) and fluorescent probes that can detect single nucleotide polymorphisms (SNPs) and insertion/ deletion (indel) polymorphisms have been designed. Furthermore, a variety of molecular clusters of dyes have also been prepared from acyclic scaffolds tethering dyes.

The synthesis, chemical, physical, biological, spectroscopic and miscellaneous analytical properties of Nalkylguanine derivatives substituted at 1-, 1,N²-, N²-, 3-, 3,N²-, 7-, 7,9- and 9-positions have been surveyed, mainly from the 2003-2009 period. Beyond the synthetic methods, particular emphasis has been given to products of mutagenesis and carcinogenesis, the role of modified fluorescent guanosines (wyosine, wyebutosine), mRNA cap structures and drugs stemming from N-alkylguanines. The review is based on 154 references and contains 64 schemes with 355 numbered structures.