Position-selective scission

Molecular Design for Position-Selective Scission of Poiymer Skeleton... 

Silylated methacrylates are also useful in positive, chain scission, bilevel deep-UV resists (30, 31). However, the silyl substituent must be carefully selected to avoid an excessive decrease in Tg. For example, pentamethyl-disiloxypropyl methacrylate has limited utility in resist applications, because it decreases the Tg (30). Copolymerization with other monomers may yield glassy, oxygen-resistant materials, but syntheses requiring controlled polymerization of three or more constituents may be unduly complicated. 

As shown in fig. 25(A), DNApi-Acr has an acridine moiety in its internal position, and is complementary with most part of the substrate RNAi. In the RNAi/DNApi-Acr hetero-duplex, only ribonucleotide U19 (in front of the acridine) is kept free from Watson-Crick base-pairing. When this system was treated with LuCb, the substrate RNA was site-selectively and efficiently hydrolyzed (lane 9 in fig. 26). The selective scission sites are the 5 -side of U-19 (major scission-site) and its 3 -side (minor scission-site), as schematically depicted in fig. 27(A). At pH 7 and 37 °C, more than half of the substrate RNA was cleaved... 

Fig. 32. Typical MALDI-TOF MS spectrum for the produets of site-selective scission of RNA from human gene by Lu(III) in presence of oligonueleotides bearing two aeridines (the sequenees are presented in (A)). The signal at m/z = 4168.8 corresponds to the 13-mer fragment (U298-C286) whieh involves a potent SNP site (the nucleotide at position 290). The signals at m/z = 3542.6 and 4787.7 are for the 5 -side fragment (G309-C299) and the 3 -side...

Radiation-sensitive polymers are used to define pattern images for the fabrication of microelectronic devices and circuits. These polymers, called resists, respond to radiation by either chain scission (positive resists) or by crosslinking (negative resists). In positive resists, the exposed areas dissolve selectively by chemical developers in negative resists, the exposed areas are insoluble and remain after development. 

A rather more complex tertracyclic indole based compound lowers blood pressure by selective blockade of a 1-adrenergic receptors. Reaction of the anion from indole (72-1) with butyrolactone (72-2) leads to the scission of the carbon-oxygen bond in the reagent and the formation of the alkylated product (72-3). The acid is then cyclized onto the adjacent 2 position to give the ketone (72-4) by treatment with a Lewis acid such as polyphosphoric acid. Reaction with bromine then leads to the brominated ketone (72-5). This is subjected to reductive alkylation with ethylene... 

To accomplish site-selective DNA scission using the non-covalent strategy, we need both (i) molecular scissors that show sufficiently high substrate-specificity and (ii) hot spots" that are formed at predetermined positions in substrate DNA and are hydrolyzed preferentially by these molecular scissors. 

An intruiging approach to site-selective RNA cleavage was reported by Kuzuya et al. [130]. In contrast to the previons examples, in this system the metal complex is free in solution (not localized). Site-selective activation for hydrolysis at single positions in a target RNA strand is achieved by covalent attachment of an acridine moiety to the template DNA strand, which canses local perturbation in the hybridized RNA strand opposite this position [131]. RNA strand scission is very site-specific for the localized perturbation (Fig. 9b). This approach was optimized for various metal ions inclnding Ca and Mg % transition metal ions, and lanthanide ions [132, 133]. Two sites in a single RNA conld be activated by incorporation of two acridines in the DNA template [134], and the rate of the process was further enhanced by the attachment of a ligand for Lu in close proximity to the acridine activator [135]. 

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