Interaction of a gold(<scp>i</scp>) dicarbene anticancer drug with human telomeric DNA G-quadruplex: solution and computationally aided X-ray diffraction analysis

Guarra, Federica; Marzo, Tiziano; Ferraroni, Marta; Papi, Francesco; Bazzicalupi, Carla; Gratteri, Paola; Pescitelli, Gennaro; Messori, Luigi; Biver, Tarita; Gabbiani, Chiara

doi:10.1039/c8dt03607a

Cited by 38 publications

(43 citation statements)

References 54 publications

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Section: Angewandte Chemiementioning

confidence: 59%

“…Zuschriften metal complex binding to quadruplexes (with structurally unrelated planar species)-two salphen complexes, [25] and two gold complexes [26,27] -with all these giving parallelstranded assemblies in the crystal, in contrast to the antiparallel arrangement reported here.T he most recently reported second gold complex structure shows adisordered end-pasted binding mode ( Figure S11). [27] We have previously used structural data to relate luminescence intensity of the "light-switch" complex [Ru(phen) 2 -(dppz)] 2+ to the degree of encapsulation of the dppz ligand. [28] While we would predict that the phenazine nitrogen atoms are at least partially blocked when bound to most duplex DNAb ase steps, [29] the crystal structure of L-2 bound to d(TCGGCGCCGA) shows that the nitrile moiety protrudes into the major groove and is thus accessible to solvent.…”

Section: Angewandte Chemiementioning

confidence: 59%

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Structural Studies Reveal Enantiospecific Recognition of a DNA G‐Quadruplex by a Ruthenium Polypyridyl Complex

et al. 2019

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By using X-rayc rystallography,w es how that the complexes L/D-[Ru(TAP) 2 (11-CN-dppz)] 2+ (TAP = 1,4,5,8tetraazaphenanthrene,d ppz = dipyridophenazine) bind DNA G-quadruplex in an enantiospecific manner that parallels the specificity of these complexes with duplex DNA. The L complex crystallises with the normally parallel stranded d(TAGGGTTA) tetraplex to give the first such antiparallel strand assembly in which syn-guanosine is adjacent to the complex at the 5' end of the quadruplex core.SRCD measurements confirm that the same conformational switch occurs in solution. The D enantiomer,b yc ontrast, is present in the structure but stacked at the ends of the assembly.I na ddition, we report the structure of L-[Ru(phen) 2 (11-CN-dppz)] 2+ bound to d(TCGGCGCCGA), ad uplex-forming sequence, and use both structural models to providei nsight into the motif-specific luminescence response of the isostructural phen analogue enantiomers.

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Section: Angewandte Chemiementioning

confidence: 59%

Section: Angewandte Chemiementioning

confidence: 59%

Structural Studies Reveal Enantiospecific Recognition of a DNA G‐Quadruplex by a Ruthenium Polypyridyl Complex

et al. 2019

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“…The Protein Data Bank contains 24 DNA crystal structures that contain Sr 2+ cations. The metals are involved in a number of interactions, for example in water-coordinated binding to a DNA duplex (PDB entry 3v06; Pallan et al, 2012), as several Sr 2+ cations coordinated to the bases as well as the phosphates of an DNA duplex (PDB entry 1wv6; Egli et al, 2005), involved in outer-shell binding to phosphates in a Holliday junction structure (PDB entry 1m6g; Thorpe et al, 2003) and participating in the crystal packing of a telomeric DNA segment containing a quadruplex motif (PDB entry 6h5r; Guarra et al, 2018). The crystal structures of A-like duplexes d(GGTCGT-CC) 2 (PDB entries 5wsp and 5gsk; Liu et al, 2017) show the same binding of Sr 2+ to the symmetry-related mismatched thymines, O4(T)Á Á ÁSr 2+ Á Á ÁO4(T)*, as we observe in the reported structures.…”

Section: Chom-18brmentioning

confidence: 99%

Structural variability of CG-rich DNA 18-mers accommodating double T–T mismatches

Kolenko¹,

Svoboda²,

Černý³

et al. 2020

Acta Cryst Sect D Struct Biol

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Solution and crystal data are reported for DNA 18-mers with sequences related to those of bacterial noncoding single-stranded DNA segments called repetitive extragenic palindromes (REPs). Solution CD and melting data showed that the CG-rich, near-palindromic REPs from various bacterial species exhibit dynamic temperature-dependent and concentration-dependent equilibria, including architectures compatible with not only hairpins, which are expected to be biologically relevant, but also antiparallel duplexes and bimolecular tetraplexes. Three 18-mer oligonucleotides named Hpar-18 (PDB entry 6rou), Chom-18 (PDB entry 6ros) and its brominated variant Chom-18Br (PDB entry 6ror) crystallized as isomorphic right-handed A-like duplexes. The low-resolution crystal structures were solved with the help of experimental phases for Chom-18Br. The center of the duplexes is formed by two successive T–T noncanonical base pairs (mismatches). They do not deform the double-helical geometry. The presence of T–T mismatches prompted an analysis of the geometries of these and other noncanonical pairs in other DNA crystals in terms of their fit to the experimental electron densities (RSCC) and their geometric fit to the NtC (dinucleotide conformational) classes (https://dnatco.datmos.org/). Throughout this work, knowledge of the NtC classes was used to refine and validate the crystal structures, and to analyze the mismatches.

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“…For mononuclear complexes, there are modelling studies rather than NMR or crystal structure evidence. There are only four other published crystal structures showing metal complex binding to quadruplexes (with structurally unrelated planar species)—two salphen complexes, and two gold complexes—with all these giving parallel‐stranded assemblies in the crystal, in contrast to the antiparallel arrangement reported here. The most recently reported second gold complex structure shows a disordered end‐pasted binding mode (Figure S11) …”

Section: Figurementioning

confidence: 55%

Structural Studies Reveal Enantiospecific Recognition of a DNA G‐Quadruplex by a Ruthenium Polypyridyl Complex

et al. 2019

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By using X‐ray crystallography, we show that the complexes Λ/Δ‐[Ru(TAP)2(11‐CN‐dppz)]2+ (TAP=1,4,5,8‐tetraazaphenanthrene, dppz=dipyridophenazine) bind DNA G‐quadruplex in an enantiospecific manner that parallels the specificity of these complexes with duplex DNA. The Λ complex crystallises with the normally parallel stranded d(TAGGGTTA) tetraplex to give the first such antiparallel strand assembly in which syn‐guanosine is adjacent to the complex at the 5′ end of the quadruplex core. SRCD measurements confirm that the same conformational switch occurs in solution. The Δ enantiomer, by contrast, is present in the structure but stacked at the ends of the assembly. In addition, we report the structure of Λ‐[Ru(phen)2(11‐CN‐dppz)]2+ bound to d(TCGGCGCCGA), a duplex‐forming sequence, and use both structural models to provide insight into the motif‐specific luminescence response of the isostructural phen analogue enantiomers.

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Interaction of a gold(i) dicarbene anticancer drug with human telomeric DNA G-quadruplex: solution and computationally aided X-ray diffraction analysis

Abstract: Solution and solid-state data give a quite clear picture for a bis carbene gold(i) complex having perspective anticancer properties.

Cited by 38 publications

References 54 publications

Structural Studies Reveal Enantiospecific Recognition of a DNA G‐Quadruplex by a Ruthenium Polypyridyl Complex

Structural Studies Reveal Enantiospecific Recognition of a DNA G‐Quadruplex by a Ruthenium Polypyridyl Complex

Structural variability of CG-rich DNA 18-mers accommodating double T–T mismatches

Structural Studies Reveal Enantiospecific Recognition of a DNA G‐Quadruplex by a Ruthenium Polypyridyl Complex

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