Neomycin, spermine and hexaamminecobalt (III) share common structural motifs in converting B- to A-DNA.
The (dG)n.(dC)n-containing 34mer DNA duplex [d(A2G15C15T2)]2 can be effectively converted from the B-DNA to the A-DNA conformation by neomycin, spermine and Co(NH3)6(3+). Conversion is demonstrated by a characteristic red shift in the circular dichroism spectra and dramatic NMR spectral changes in chemical shifts. Additional support comes from the substantially stronger CH6/GH8-H3'NOE intensities of the ligand-DNA complexes than those from the native DNA duplex. Such changes are consistent with a deoxyribose pucker transition from the predominate C2'-endo (S-type) to the C3'-endo (N-type). The changes for all three ligand-DNA complexes are identical, suggesting that those three complex cations share common structural motifs for the B- to A-DNA conversion. The A-DNA structure of the 4:1 complex of Co(NH3)6(3+)/d(ACCCGCGGGT) has been analyzed by NOE-restrained refinement. The structural basis of the transition may be related to the closeness of the two negatively charged sugar-phosphate backbones along the major groove in A-DNA, which can be effectively neutralized by the multivalent positively charged amine functions of these ligands. In addition, ligands like spermine or Co(NH3)6(3+) can adhere to guanine bases in the deep major groove of the double helix, as is evident from the significant direct NOE cross-peaks from the protons of Co(NH3)6(3+) to GH8, GH1 (imino) and CH4 (amino) protons. Our results point to future directions in preparing more potent derivatives of Co(NH3)6(3+) for RNA binding or the induction of A-DNA.
Robinson
H
H
Biophysics Division and Department of Cell and Structural Biology, University of Illinois at Urbana-Champaign, IL 61801, USA.
Wang
A H
AH
D001483:Base Sequence; D003035:Cobalt / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009355:Neomycin / Q000378:metabolism*; D009690:Nucleic Acid Conformation / Q000187:drug effects; D017421:Sequence Analysis; D013096:Spermine / Q000378:metabolism*
C030862:cobalt ammonium complex; D013096:Spermine; D003035:Cobalt; D004247:DNA; D009355:Neomycin