Nucleosides with unusual bases

An unusual one-pot procedure for the synthesis of ribonucleoside 5 -triphosphates has been reported that is based on use of the Yoshikawa intermediate (72, Scheme 10). Treatment of the unprotected nucleoside with phosphoryl chloride in triethylphosphate and subsequent addition of tri-/i-butylammonium phosphate in DMF, gave, after aqueous work-up, the triphosphate in good yield (>60%). The reaction is thought to proceed via the intermediacy of a cyclic metatriphosphate (73) which was initially proposed by Michelson and Todd. A fully protected 2 -0-methyl ribonucleoside bound to a controlled-pore glass support via the 3 -... 

Unlike the (3-lactones and (3-lactams, the mode of action of the unusual C-glucosyl nucleoside-based natural product showdomycin is unknown. Nevertheless, this compound has been shown to possess potent antibiotic properties, with results obtained in vitro suggesting a role as a suicide inhibitor of uridine metabolism [11]. Isolated from the bacteria Streptomyces showdoensis, showdomycin contains an electrophilic moiety, malaimide, in place of the base (cf. the structures of uridine or pseudouridine). 

This non-canonical fold, established according to chemical and enzymatic structure probing, includes an extended amino acid acceptor stem, an extra large loop instead of the T-stem and loop, and an anticodon-like domain. Hence, one or several of the six modified nucleosides are required and are responsible for its cloverleaf structure. In a further study a chimeric tRNA with the sole modification of 1-methyladenosine in position 9 was synthesized it was demonstrated that this chimeric RNA folds correctly [27]. Thus, because of Watson-Crick base-pair disruption, a single methyl group is sufficient to induce the cloverleaf folding of this unusual tRNA sequence. 

This can be accounted for by the wobble hypothesis it appears that when a codon in mRNA interacts with the anticodon, unconventional pairing can form between the base in the third position of the codon (3 end of triplet) and the first position of the anticodon. The unusual nucleoside inosine (Chap. 7) frequently occurs in the latter position, and it can pair with A, U, or C. The possibility of more than one type of pairing in this position accounts for the fact that when there is more than one codon for a single amino acid (called synonyms, see Table 17.1), the differences are usually in the third position only. 

The first base of an anticodon determines whether a particular tRNA molecule reads one, two, or three kinds of codons C or A (one codon), U or G (two codons), or I (three codons). Thus, part of the degeneracy of the genetic code arises from imprecision (wobble) in the pairing of the third base of the codon with the first base of the anticodon. We see here a strong reason for the frequent appearance of inosine, one of the unusual nucleosides, in anticodons. Inosine maximizes the number of codons that can be read by a particular tRNA molecule. The inosines in tRNA are formed by deamination of adenosine after synthesis of the primary transcript. 

In contrast to Mg + and Mn +, which stabilize secondary structures in DNA and RNA, Cu + destabilizes DNA and RNA double helices, and this is attributed to the ability of copper to bind to the nucleic acid bases. Chao and Kearns have recently explored the possibility that this binding, as detected by electron and nuclear magnetic resonance spectroscopy, might be used to probe certain structural features of nucleic acid molecules, such as the looped out regions of tRNAs. The nature of the Cu complexes formed with nucleosides and nucleotides varies with the specific nucleic acid derivatives used and also the pH. Thus, in the pH range 8.5—10.0, copper forms a water-soluble complex with the ribose OH groups of the ribonu-cleosides and 5 -ribonucleotides, but these complexes cannot form with any of the deoxynucleosides or the 2 - and 3 -ribonucleotides. It is suggested that copper(ii) could stabilize unusual polynucleotide structures or interactions in certain enzymatic systems the latter could, for example, be responsible for translational errors in the RNA,DNA polymerase system which are known to be induced by transition metals. 

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