The Solution Structure of [d(CGC)r(amamam)d(TTTGCG)]2 |
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Authors: | Ya-Ping Tsao Lian-Yong Wang Shang-Te Hsu Moti L Jain Shan-Ho Chou Wen-Chang Huang Jya-Wei Cheng |
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Institution: | (1) Division of Structural Biology and Biomedical Science, Department of Life Science, National Tsing Hua University, Hsinchu, 300, Taiwan, Republic of China;(2) Department of Chemistry, National Taiwan Normal University, Taipei, Taiwan, Republic of China;(3) Institute of Biochemistry, National Chung Hsing University, Taichung, 400, Taiwan, Republic of China |
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Abstract: | The solution structure and hydration of a DNA RNA hybrid chimeric duplex d(CGC)r(amamam)d(TTTGCG)]2 in which the RNA adenines were substituted by 2 -O-methylated riboadenines was determined using two-dimensional NMR, simulated annealing, and restrained molecular dynamics. Only DNA residue 7T in the 2 -OMe-RNA DNA junction adopted an O4 -endo sugar conformation, while the other DNA residues including 3C in the DNA 2 -OMe-RNA junction, adopted C1 -exo or C2 -endo conformations. The observed NOE intensity of 2 -O-methyl group to H1 proton of 4am at the DNA 2 -OMe-RNA junction is much weaker than those of 5am and 6am. The 2 -O-methyl group of 4am was found to orient towards the minor groove in the trans domain while the 2 -O- methyl groups of 5am and 6am were found to be in the gauche (+) domain. In contrast to the long-lived water molecules found close to the RNA adenine H2 and H1 protons and the methyl group of 7T in the RNA-DNA junction of d(CGC)r(aaa)d(TTTGCG)]2, there were no long-lived water molecules found in d(CGC)r(amamam)d(TTTGCG)]2. This is probably due to the hydrophobic enviroment created by the 2 -O-methylated riboadenines in the minor groove or due to the wider minor groove width in the middle of the structure. In addition, the 2 -O-methylation of riboadenines in pure chimeric duplex increses its melting temperature from 48.5 °C to 51.9 °C. The characteristic structural features and hydration patterns of this chimeric duplex provide a molecular basis for further therapeutic applications of DNA RNA hybrid and chimeric duplexes with 2 -modified RNA residues. |
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Keywords: | 2 -OMe RNA" target="_blank">gif" alt="prime" align="BASELINE" BORDER="0">-OMe RNA DNA RNA" target="_blank">gif" alt="bull" align="MIDDLE" BORDER="0">RNA NMR solution structure |
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