Application of RNA-DNA Duplex Base Triplets to Antisense Drugs
- 1 Nanjing University, China
Sixty-four sets of three-dimensional models of RNA-DNA duplex base triplets were constructed based on codons by homology modeling method using software InsightII on Indigo workstation, which should be helpful for the study of RNA-DNA annealing, the basis of nucleic acids interactions and some peculiar motifs for design antisense oligonucleotides. Our research result reveal that the energies (such as E, Ec, Eb, Et and Enr) of DNA/asRNA hybrids are lower than those of RNA/asDNA hybrids while the energies (such as En and End) of DNA/asRNA hybrids are higher than those of RNA/asDNA hybrids for most binary complex and ternary complex, especially E, Ec, Eb and En in evidence. And the total energy of GGG/CCC hybrid is the lowest of all the hybrids, the more G/C base pairs, the lower of energy of the triplet hybrid and (G/C)3<U(G/C)2<A(G/C)2 <U2(G/C)<AU(G/C)<A2(G/C) in turn; the U-including hybrid system stability, the more of number of uracil (U), the lower of energy of the triplet hybrid; the energy of GU-including hybrid is lower than that of CU-including hybrid no matter for binary complex or ternary complex. G/A/U bases often deviate from base pair planes, which can form hydrogen bonds with neighboring base pairs and affects the stabilities of triplets. Moreover, some peculiar oligodeoxynucleotide sequence motifs that could be derived from corresponding triplet hybrids are divided into two groups: four-member motif and five - member motif, where the former comprises eight motifs, namely 5'-TCTT-3',5'-TGCT-3',5'-CCTT-3',5'-CCAT-3', 5'-CATC-3', 5'-ATCT-3', 5'-GCTG-3' and 5'-GTCT-3'; and the later consists of four motifs, viz 5'-TGCTG-3', 5'-GTCTT-3', 5'-CCATC-3' and 5'-CATCT-3', which are positively correlated with antisense activities and play an important role in designing antisense drugs.
Copyright: © 2005 Jie Yang, Yao Leng and Ju Bao. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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- RNA-DNA hybrid triplets
- peculiar sequence motif
- antisense oligodeoxynucleotides