Application of RNA–DNA duplex base triplets to antisense drugs

Abstract

The 64 RNA–DNA duplex base triplets 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, E c, E b, E t, and E nr) of DNA/asRNA hybrids are lower than those of RNA/asDNA hybrids while the energies (such as E n and E nd) of DNA/asRNA hybrids are higher than those of RNA/asDNA hybrids for most binary complex and ternary complex, especially E, E c, E b, and E n in evidence. And the total energy of GGG/CCC hybrid is the lowest of all the hybrids, the more of number of G/C base pair, the lower of energy of the triplet hybrid, and (G/C) 3<U(G/C) 2<A(G/C) 2<U 2(G/C)<AU(G/C)<A 2(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 sequence motifs that could be derived from useful triplet hybrids above, namely CCAC, TCCC, ACTC, ATCC, GCCA, CTCT, CACC, CCCA, TGCT, TGCC, TCTT, and TCCTT, are positively correlated with antisense activities. The former six motifs are the same of Gesteland's results, and the later six motifs are new discovered motifs by us, which proved by Arnedo's, Zewert's, and Zhang's results, which play an important role in designing antisense drugs.