NMR studies of an oligonucleotide with an unusual structure induced by platinum anticancer drugs

Kline, Tammy Page; Marzillï, Luigi G.; Live, David; Zon, Gerald

doi:10.1016/0006-2952(90)90184-m

Cited by 14 publications

(9 citation statements)

References 29 publications

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“…Such studies require that factors influencing hairpin structure be well established. Our investigations have shown that ZnZ+ and Pt anticancer drugs are able to control the duplex-hairpin equilibrium of self-complementary oligonucleotides (Kline et al, 1990 ;Jia et al, 1991 ;Iwamoto et al, 1994). The Pt derivative has an unusual conformation.…”

mentioning

confidence: 82%

Similar Conformations of Hairpins with TTT and TTTT Sequences NMR and Molecular Modeling Evidence for T · T base pairs in the TTTT hairpin

Kuklenyik

Yao

Marzillï

1996

European Journal of Biochemistry

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"P signals of the two hairpins have been nearly completely assigned by means of two-dimensional NMR spectroscopy in D,O (NOESY (two-dimensional nuclear Overhauser effect and exchange spectroscopy) at mixing times of 5, 50, 100, 300 and 500 ms, double-quantum-filtered correlation spectroscopy (DQF-COSY) and 'H-"P reverse chemical shift correlation (RCSC), and one-dime,nsional NOE spectra in 90% H,O. Conformational analysis using distance geometry (DG), molecular mechanics (MM) and molecular dynamics (MD) gave model conformations, which were evaluated by comparison of experimental and simulated 2D NOESY spectra. For the T, sequence in T4, both NMR data and modeling indicated a T(a) . (5) of T3] has a gauche', gauche' <,a conformation with a trans y angle for the second residue in both. These or similar features appear to be present in most of the few other hairpins studied previously by conformational methods. Thus, we believe that the conformations of the loops in T, and T, hairpins have greater similarities than previously recognized.

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mentioning

confidence: 82%

Similar Conformations of Hairpins with TTT and TTTT Sequences NMR and Molecular Modeling Evidence for T · T base pairs in the TTTT hairpin

Kuklenyik

Yao

Marzillï

1996

European Journal of Biochemistry

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“…These data indicate that in the platinated duplexes the helix axis is kinked at the platination site. The Pt-GG adduct in hairpins was studied by Kline et al (1990) and Yohannes et al (1993). The Pt-GG adduct in hairpins was studied by Kline et al (1990) and Yohannes et al (1993).…”

Section: Poymentioning

confidence: 99%

“…Furthermore, the sugar ring of the 5' platinated-guanine adopts an N conformation (roughly 3'-endo, 2'-exo) (Altona, 1982). The Pt-GG adduct in hairpins was studied by Kline et al (1990) and Yohannes et al (1993).…”

Section: Poymentioning

confidence: 99%

The Solution Structure of a DNA Duplex Containing the cis ‐Pt(NH₃)₂[d(‐GTG‐)‐N 7(G), N 7(G)] Adduct, as Determined with High‐Field NMR and Molecular Mechanics/Dynamics

Garderen

Houte

1994

European Journal of Biochemistry

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The solution structure of the cis-Pt-GTG adduct in the double-stranded oligomer d(CTCTAGTGCTCAC).td(GTGAGCACTAGAG) was studied with high-resolution NMR techniques. For model building, the distance information obtained from two-dimensional NOE experiments was used in molecular mechanic computations and molecular dynamic structure refinements. The structural distortion upon platination appears to be restricted to the base pairs Pt-G6.C21 and T7.A20; Pt-G8.C19 forms a normal Watson-Crick base pair. T7 is positioned in the minor groove and stacks with the highly propeller-twisted Pt-G6. There is no hydrogen bonding between T7 and A20. The complementary strand is undistorted; A20 stacks with its flanking cytidines (C19 and C21) as in regular B-DNA. The duplex is locally unwound (from base pair A5.T22 to G8.C19: 19 degrees) and is slightly kinked (20 degrees) at the platination site. The platinum coordination distorts the DNA structure at the 5' side of the platinated-GTG-sequence and changes the minor groove face.

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“…We have shown that Zn 2+ , Mg 2+ , and Pt anticancer drugs are capable of controlling the hairpin−duplex equilibrium of oligos. − The interaction of these metals with d(ATGGGATCCCAT) and d(ATGGGTTCCCAT) was studied by using 2D NMR spectroscopy . The first sequence forms a duplex at 12 °C.…”

Section: Introductionmentioning

confidence: 99%

Mercury(II) Site-Selective Binding to a DNA Hairpin. Relationship of Sequence-Dependent Intra- and Interstrand Cross-Linking to the Hairpin−Duplex Conformational Transition

1996

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Hg(II) interacted site selectively with only one of three deoxyribooligonucleotides examined; these "oligos" each had a different number of unmatched T residues. Thus, Hg(II) formed an intrastrand T-Hg-T cross-link between the first and fourth T residues of the hairpin, d(GCGCTTTTGCGC) (T4). The DNA strand formed a loop around the Hg, as if the Hg atom had been lassoed. The interactions of Hg(II) with two other oligos, d(ATGGGTTCCCAT) (T2) and d(GCGCTTTGCGC) (T3), were less specific. Previously, we found that at high DNA and salt concentrations, T2 was a mixture of hairpin and duplex forms while T3 and T4 had the hairpin form; modeling studies showed that in the free T4 hairpin the two T's at the ends of the (T)(4) loop form a T.T wobble base pair. Only in T4 are the T residues positioned to form an intrastrand cross-link readily. The Hg(II)-oligo adducts formed as a function of added Hg(II) were investigated by titrations monitored by UV, CD, and (1)H NMR spectroscopy. The appearance of a new set of (1)H signals with the concomitant decay of the free oligo (1)H signals indicated that 1:1 Hg(II):T2, 1.5:1 Hg(II):T3, and 1:1 Hg(II):T4 adducts were formed with Hg(NO(3))(2). In H(2)O, these adducts all had spectra with very downfield signals for the exchangeable TN(3)H and GN(1)H groups, a characteristic of base-paired regions. All upfield N(3)H signals from the (T)(2) and (T)(3) sequences of the free oligo disappeared in the spectra of the 1:1 Hg(II):T2 and 1.5:1 Hg(II):T3 adducts. The disappearance of the NH signals, the UV spectral changes, and the stoichiometries (1:1 Hg(II):T2 and 1.5:1 Hg(II):T3) indicate that these adducts are duplexes containing two and three T-Hg-T interstrand cross-links for T2 and T3, respectively. The (1)H and (13)C signals of the 1:1 Hg(II):T4 adduct in D(2)O were nearly completely assigned by 2D NMR spectroscopy. The spectrum of the adduct in H(2)O had only two of the four original TN(3)H signals from the (T)(4) sequence present in the spectrum of T4; this result is consistent with the presence of a TN3-Hg-TN3 cross-link. The (13)C chemical shift changes upon Hg(II) binding indicated that the TN3-Hg-TN3 cross-link was between the T's at each end of the (T)(4) loop. The NOESY, CD, and UV spectra were all consistent with a hairpin conformation for the 1:1 Hg(II):T4 adduct. A hairpin conformation also appeared reasonable from molecular modeling calculations. In conclusion, the length of the central (T)(n)() sequence influenced the type of T-Hg-T cross-link formed and, in turn, the conformation of the adducts. For (T)(2) and (T)(3), interstrand T-Hg-T cross-linking favored the duplex form. In contrast, for (T)(4), intrastrand T-Hg-T cross-linking stabilized the hairpin form.

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NMR studies of an oligonucleotide with an unusual structure induced by platinum anticancer drugs

Cited by 14 publications

References 29 publications

Similar Conformations of Hairpins with TTT and TTTT Sequences NMR and Molecular Modeling Evidence for T · T base pairs in the TTTT hairpin

Similar Conformations of Hairpins with TTT and TTTT Sequences NMR and Molecular Modeling Evidence for T · T base pairs in the TTTT hairpin

The Solution Structure of a DNA Duplex Containing the cis ‐Pt(NH₃)₂[d(‐GTG‐)‐N 7(G), N 7(G)] Adduct, as Determined with High‐Field NMR and Molecular Mechanics/Dynamics

Mercury(II) Site-Selective Binding to a DNA Hairpin. Relationship of Sequence-Dependent Intra- and Interstrand Cross-Linking to the Hairpin−Duplex Conformational Transition

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NMR studies of an oligonucleotide with an unusual structure induced by platinum anticancer drugs

Cited by 14 publications

References 29 publications

Similar Conformations of Hairpins with TTT and TTTT Sequences NMR and Molecular Modeling Evidence for T · T base pairs in the TTTT hairpin

Similar Conformations of Hairpins with TTT and TTTT Sequences NMR and Molecular Modeling Evidence for T · T base pairs in the TTTT hairpin

The Solution Structure of a DNA Duplex Containing the cis ‐Pt(NH3)2[d(‐GTG‐)‐N 7(G), N 7(G)] Adduct, as Determined with High‐Field NMR and Molecular Mechanics/Dynamics

Mercury(II) Site-Selective Binding to a DNA Hairpin. Relationship of Sequence-Dependent Intra- and Interstrand Cross-Linking to the Hairpin−Duplex Conformational Transition

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The Solution Structure of a DNA Duplex Containing the cis ‐Pt(NH₃)₂[d(‐GTG‐)‐N 7(G), N 7(G)] Adduct, as Determined with High‐Field NMR and Molecular Mechanics/Dynamics