Structural features of a central mismatch in oligonucleotide hybrid duplexes visualized via Raman spectroscopy: model system for evaluation of potential "antisense" drugs.
Structural features of mismatched base pairs were studied on four nonamer hybrid duplexes formed between the 5'-d(GTGATATGC)-3' complement and its 5'-r(GCAUNUCAC)-3' (N = A, C, G, U) counterparts. This oligonucleotide set is considered a model molecular system for future systematic studies of various modifications of internucleotide linkages with respect to their impact on the structure of mismatched base pairs. Raman spectra, measured at 15 degrees C, revealed the prevailing A-like structure of the RNA strand and mixed A-like and B-like characteristics for the DNA strand. All three mismatches disturb only weakly the overall conformation of the hybrid duplex in contrast to analogous mismatched DNA duplexes. In particular, the dT x rG mismatch influences the global hybrid duplex geometry almost negligibly. The dT x rC and dT x rU mismatches induce somewhat more pronounced distortions of the backbone structure and of the thymine position, the latter being expressed by a change of the surrounding methylene group without effect on the carbonyl's vibrations. Structural effects of the mismatches correlate well with the duplex thermodynamic stabilities obtained by ultraviolet (UV) absorption, i.e., the dT x rG mismatch decreases the hybrid duplex stability very weakly while the effect of both pyrimidine-pyrimidine mismatches is considerable.
Nemecek
Daniel
D
Université P. et M. Curie, L.P.B.C. (CNRS UMR 7033), 4 place Jussieu, Case 138, F-752 52 Paris Cedex 05, France. nemecek@karlov.mff.cuni.cz
Vaisocherová
Hana
H
Stepánek
Josef
J
Turpin
Pierre-Yves
PY
D020137:Base Pair Mismatch; D015195:Drug Design; D004341:Drug Evaluation; D009690:Nucleic Acid Conformation; D009692:Nucleic Acid Heteroduplexes / Q000737:chemistry*; D016376:Oligonucleotides, Antisense / Q000737:chemistry*; D013059:Spectrum Analysis, Raman; D013816:Thermodynamics
D009692:Nucleic Acid Heteroduplexes; D016376:Oligonucleotides, Antisense