A novel DNA structure induced by the anticancer bisplatinum compound crosslinked to a GpC site in DNA

Danzhou Yang; Stella S.G.E. van Boom; Jan Reedijk; Jacques H. van Boom; Nicholas Farrell; Andrew H.J. Wang

doi:10.1038/nsb0795-577

A novel DNA structure induced by the anticancer bisplatinum compound crosslinked to a GpC site in DNA

Danzhou Yang
, Stella S.G.E. van Boom
, Jan Reedijk
, Jacques H. van Boom
, Nicholas Farrell
, Andrew H.J. Wang

Research output: Contribution to journal › Article › peer-review

72 Scopus citations

Abstract

The bifunctional platinum compound, [{trans-PtCI(NH₃)₂}₂(H₂N(CH₂)₄NH₂)]₂+f forms a stable adduct with the self-complementary DNA oligomer CATGCATG, with the two platinum atoms coordinated at the N₇ positions of the two symmetrical G4 nucleotides. The NMR-derived structure shows that the DNA octamer forms a novel hairpin structure with the platinated G₄ residue adopting a syn conformation and the guanine base in the minor groove. Two such hairpins stack end-over-end and are linked together by the butanediamine tether to form a dumbbell structure. Such unusual structural distortion is different from that of the anticancer drug cisplatin-DNA adduct and may provide clues to explain the distinct biological activities of the two compounds.

Original language	English (US)
Pages (from-to)	577-586
Number of pages	10
Journal	Nature Structural Biology
Volume	2
Issue number	7
DOIs	https://doi.org/10.1038/nsb0795-577
State	Published - Jul 1995
Externally published	Yes

ASJC Scopus subject areas

Structural Biology
Biochemistry
Genetics

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title = "A novel DNA structure induced by the anticancer bisplatinum compound crosslinked to a GpC site in DNA",

abstract = "The bifunctional platinum compound, [\{trans-PtCI(NH3)2\}2(H2N(CH2)4NH2)]2+f forms a stable adduct with the self-complementary DNA oligomer CATGCATG, with the two platinum atoms coordinated at the N7 positions of the two symmetrical G4 nucleotides. The NMR-derived structure shows that the DNA octamer forms a novel hairpin structure with the platinated G4 residue adopting a syn conformation and the guanine base in the minor groove. Two such hairpins stack end-over-end and are linked together by the butanediamine tether to form a dumbbell structure. Such unusual structural distortion is different from that of the anticancer drug cisplatin-DNA adduct and may provide clues to explain the distinct biological activities of the two compounds.",

author = "Danzhou Yang and \{van Boom\}, \{Stella S.G.E.\} and Jan Reedijk and \{van Boom\}, \{Jacques H.\} and Nicholas Farrell and Wang, \{Andrew H.J.\}",

year = "1995",

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doi = "10.1038/nsb0795-577",

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volume = "2",

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T1 - A novel DNA structure induced by the anticancer bisplatinum compound crosslinked to a GpC site in DNA

AU - Yang, Danzhou

AU - van Boom, Stella S.G.E.

AU - Reedijk, Jan

AU - van Boom, Jacques H.

AU - Farrell, Nicholas

AU - Wang, Andrew H.J.

PY - 1995/7

Y1 - 1995/7

N2 - The bifunctional platinum compound, [{trans-PtCI(NH3)2}2(H2N(CH2)4NH2)]2+f forms a stable adduct with the self-complementary DNA oligomer CATGCATG, with the two platinum atoms coordinated at the N7 positions of the two symmetrical G4 nucleotides. The NMR-derived structure shows that the DNA octamer forms a novel hairpin structure with the platinated G4 residue adopting a syn conformation and the guanine base in the minor groove. Two such hairpins stack end-over-end and are linked together by the butanediamine tether to form a dumbbell structure. Such unusual structural distortion is different from that of the anticancer drug cisplatin-DNA adduct and may provide clues to explain the distinct biological activities of the two compounds.

AB - The bifunctional platinum compound, [{trans-PtCI(NH3)2}2(H2N(CH2)4NH2)]2+f forms a stable adduct with the self-complementary DNA oligomer CATGCATG, with the two platinum atoms coordinated at the N7 positions of the two symmetrical G4 nucleotides. The NMR-derived structure shows that the DNA octamer forms a novel hairpin structure with the platinated G4 residue adopting a syn conformation and the guanine base in the minor groove. Two such hairpins stack end-over-end and are linked together by the butanediamine tether to form a dumbbell structure. Such unusual structural distortion is different from that of the anticancer drug cisplatin-DNA adduct and may provide clues to explain the distinct biological activities of the two compounds.

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A novel DNA structure induced by the anticancer bisplatinum compound crosslinked to a GpC site in DNA

Abstract

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