Enantiomeric nucleic acids

Thus, enantiomeric nucleic acids which are composed of mirror image nucleo-... 

Buta-1,3-diene (10.101, Fig. 10.24) is a gaseous chemical used heavily in the rubber and plastics industry, the presence of which in the atmosphere is also a concern. Butadiene is suspected of increasing the risks of hematopoietic cancers, and it is classified as a probable human carcinogen. Butadiene must undergo metabolic activation to become toxic the metabolites butadiene monoepoxide (10.102, a chiral compound) and diepoxybutane (10.103, which exists in two enantiomeric and one meso-form) react with nucleic acids and glutathione [160 - 163], as does a further metabolite, 3,4-epoxybutane-l,2-diol (10.105). Interestingly, butadiene monoepoxide is at least tenfold more reactive than diepoxybutane toward nucleic acids or H20. Conjugation between the C=C bond and the oxirane may account for this enhanced reactivity. 

RDCs are commonly used for the structure elucidation of proteins and nucleic acids nowadays. Only recently the approach was transferred back to also obtain structural information of small- to medium-sized organic molecules. The central application in this case is the determination of relative configurations of distant chiral and prochiral centres, and also conformational studies of biologically active molecules, for example the enantiomeric differentiation of small molecules in chiral alignment media can be achieved. 

Enantiomeric Mannich bases may be obtained either by using optically active starting materials or by optical resolution of racemic derivatives. In the former case, the reactants are mostly provided by natural products, such as components of essential oils (e.g., camphor ), hormones, nucleic acids, employed as substrates, or a-amino acids - mainly used as amine reagents, etc. A list of optically active reactants reported in the literature is summarized in Table 12. 

Peptides and proteins represent, apart from the nucleic acids, the most important class of compounds governing the basic biochemical principles in nature. During the last hundred years the synthesis of natural and unnatural amino acids as well as peptide synthesis has experienced a breathtaking development. The interest in this process has grown as the knowledge about the relationship between the structure of peptides and proteins and their physiological effects has increased. Nowadays the chemist may refer to a variety of synthetic methods to prepare enantiomerically enriched or pure a-amino acids (for an overview see [1]). Nevertheless, the need for amino acids with a very special substitution pattern often reveals the limits of the established methods. Consequently, the development of new synthetic routes to a-amino acids (and, naturally, also to 8-amino acids, which have enjoyed increased attention over the last years) is playing an important role in the current chemical research. This chapter reviews the application of a special part of radical chemistry in the synthesis and modification of amino acids and peptides, namely reactions that proceed via diradicals. 

Interest continues in conformationally-locked bicyclic nucleosides and their oligomers. A report from Wengel s laboratory describes details of the synthesis of the a-L-LNA (locked nucleic acid) nucleoside 129, in which a key step is the treatment of ditosylate 128 with NaOH in aqueous ethanol to establish the bicycle, a reaction thought to involve a 2,2 -anhydronucleoside as an intermediate. Also reported is the similar conversion of 130 into the a-L-xy/o-LNA nucleoside 131." The effect on RNA binding of the incorporation of these two compounds, and the previously-prepared P-D-xyfo-isomer and LNA nucleoside itself, into oligonucleotides has been studied the behaviour of the other four stereoisomers of LNA, enantiomeric with those synthesized, was also studied... 

By this highly sensitive and selective method, subpicomolar of a specific protein can be detected [56], and the procedure can be used to detect a wide range of proteins. The same concept has also been used for specific detection of potassium ions [56] and for enantiomeric resolution of nucleic acids [25], and might be used for identification of a wide range of molecules as well as for HTS for drug discovery. 

Enantiomers are stereoisomers that are nonsuperposable mirror images. The significance of enantiomerism is that, except for inorganic and a few simple organic compounds, the vast majority of molecules in the biological world show this type of isomerism, including carbohydrates (Chapter 17), lipids (Chapter 19), amino acids and proteins (Chapter 18), and nucleic acids (DNA and RNA, Chapter 20). Further, approximately one-half of the medications used in human medicine also show this type of isomerism. 

The only stereogenic centers of DNA and RNA are found at the sugar carbons, and because the ribose or deoxyribose are enantiomerically pure, natural nucleic acids are isotactic. The P of the phosphodiester backbone of a nucleic acid is not a stereogenic center, but the two 0 groups of a connecting phosphate are diastereotopic. The phosphorus is thus prochi-ral. This has led to the use of labeled phosphates in mechanistic studies, as described with one example in a Connections highlight on the next page. 

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