Hydrogen-bonding preferences in 2,6-diaminopurine: uracil (thymine) and 8-methyl adenine:uracil (thymine) complexes.
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The existence of the complexes poly[r(s4U)] . poly[r(n2h6A] and poly-[r(s4U)] . poly[r(n2A)] was demonstrated by means of spectrophotometric titration and sedimentation veolicty analysis. According to the absorption-temperature profiles thioketo substitution of poly[r(U)] . poly[r(n2h6A)] led to stabilisation of the helical structure, thus implying that the 4-thioketo group does not participate in s4U . n2h6A base pairing. In the case of poly[r(s4U)] . poly[r(n2A)] drastic destabilistaion of the helical structure by thioketo substitution was observed. This indicates that the thioketo substituents participate in s4U .n2A base pairing.
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The in vitro cytotoxicity of 6 amino-5 formylmethylamino-1,3 dimethyluracil (ADMU) a major metabolite of caffeine in rats was studied by cell counts or [3H]thymidine incorporation in the murine Lewis lung carcinoma (3LL) and L929 fibroblast cells and in the human E cell line derived from an ovarian carcinoma. Unlike 5-fluorouracil (5FU) which was markedly cytotoxic, ADMU concentrations up to 60 micrograms/ml were devoid appreciable cytocidal action. Similarly, 1-10 micrograms 5FU markedly inhibited the blastogenic response of rat lymphocytes to PHA, whereas lymphoproliferation was not affected at ADMU concentrations up to 100 micrograms/ml. In vivo administration of ADMU (40 mg/kg, twice a day on day 1 to 3) to L1210 leukaemia-bearing mice caused a transient short-lasting reduction of tumour cell numbers only on day 6 after leukaemia inoculation.U
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The interaction between ant (antirepressor) mRNA and its antisense RNA, sar (small antisense RNA), is important in regulation of the development of bacteriophage P22. Sar is 68-69 nucleotides in length and is believed to consist of two hairpin structures separated by a small inter-hairpin region, followed by a short 3' tail [Schaefer and McClure RNA 1997, 3, 141-156]. A novel feature of the proposed secondary structure of the first hairpin is a extremely rare triple U:U base stack. Heteronuclear NMR studies presented here show that the first hairpin does not possess a unique structure in the absence of the second hairpin. However, it acquires a well-defined structure within full length sar. Remarkably, the triple U:U stack appears to be a stable feature of the first hairpin, regardless of the presence or absence of the second hairpin.
The crystal structure of the RNA dodecamer 5'-GGACUUUGGUCC-3' has been determined from X-ray diffraction data to 2.6 A resolution. This oligomer forms an asymmetric double helix in the crystal. Four consecutive non-Watson-Crick base-pairs are formed in the middle of the duplex including the first intrahelical U-U (or T-T) pairs observed in an oligonucleotide crystal structure. Two different conformations of U-U pairs are observed in the context of the surrounding sequence. One of these pairs is highly twisted, allowing a bound water to bridge across strands in the major groove. The crystal packing illustrates a new form of RNA helix-helix interaction.
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