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The intrinsic dynamic and architectural flexibility of DNA and RNA, resulting in to specific function, are the result of cooperative interplay of pentofuranose, nucleobase and phosphodiester moieties. We have earlier shown [see list of publications in http://www.boc.uu.se/] that the interplay of various stereoelectronic gauche and anomeric and associated steric effects energetically drive the sugar-phosphate conformation, which, in turn, is dictated by the electronic nature of the aglycone and other substituents of the sugar ring. Following three independent sets of experiments show that the stereoelectronic forces indeed play a significant role in the transmission of conformational information in DNA and RNA beside stacking, H-bonding and electrostatics:
(1) Using guanosine 3',5'-bis-ethylphosphate as a model mimicking the central nucleotide moiety in a trinucleoside diphosphate in a single stranded RNA (i.e. in complete absence of any intramolecular base-base stacking), we have shown that a complete interdependency of conformational preference of sugar and phosphate backbone exists in ribonucleoside 3'- ethylphophate as the of protonation-deprotonation equilibrium of the aglycone changes as a function of pH. It has been shown that the mechanism of intramolecular conformational transmission is simply governed by appropriate overlap of donor-acceptor orbitals dictated by the electronegativity of various sugar substituents [Angew Chem. Int. Ed. 38, 3645-3650 (1999) (PDF:301).; J. Phys. Org. Chem., 13, 300-305 (2000) (PDF:310)].
(2) A single-point substitution of the O4'-oxygen by a CH2 group at the sugar residue of A6 (i.e. 2'-deoxyaristeromycin moiety) in a self-complementary DNA duplex, 5'- d(C1 G2 C3 G4 A5 A6 T7 T8 C9 G10 C11 G12)2-3', has been shown to steer the fully Watson-Crick basepaired DNA duplex (1A) to a doubly A6:T7 Hoogsteen basepaired (1B) B-type DNA duplex, resulting in a dynamic equilibrium of (1A) (1B): Keq = k1/k-1 = 0.56 ± 0.08 [k1 (298K) = 3.9 ± 0.8 sec-1; DH° = 164 ± 4 kJ/mol; -TDS° (298K) = -92 kJ/mol giving a of 72 kJ/mol. Ea (k1) = 167 ± 14 kJ/mol] compared to the reverse conversion of the Hoogsteen (1B) to the Watson-Crick (1A) structure [k-1 (298K) = 7.0 ± 0.6 sec-1, DH° = 153 ± 13 kJ/mol; -TDS (298K) = -82 kJ/mol giving a of 71 kJ/mol. Ea (k-1) = 155 ± 13 kJ/mol]. A comparison of of the forward (k1) and backward (k-1) conversions, (1A) (1B), shows that there is ca 1 kJ/mol preference for the Watson-Crick (1A) over the double Hoogsteen basepaired (1B) DNA duplex, thus giving an equilibrium ratio of almost 2:1 in favour of the fully Watson-Crick basepaired duplex [J. Biomolecular Struct & Dyn, 18, 783, 2001 (PDF:320)].
(3) Finally, the sensitivity of the RNase H has been explored to map
the local structural changes in the antisense oligo (AON)/RNA hybrids,
containing a single 1-(1',3'-O-anhydro-b-D-
psicofuranosyl)thymine with locked 3'-endo sugar conformation at different
sites of AON. This has revealed that the local conformational changes brought
by the constrained nucleoside, although invisible by CD (global structure
unaltered from that of the native counterpart), span in the hybrid as far
as 5 nucleotides toward the 5'-end of the AONs (3'-end of RNA), showing
the unique transmission of the structural distortion from a single modification
site [Tetrahedron Letters, 41, 8601 (2000), (PDF:313,