Novel in situ methodology to observe the interactions of chemotherapeutical Pt drugs with DNA under physiological conditions.
The binding of the antitumor drug cisplatin with DNA was determined by means of in situ resonant inelastic X-ray scattering (RIXS) spectroscopy. Because of the penetrating properties of hard X-rays, we could determine, under physiological conditions, the identity and number of platinum complexes present. In situ RIXS revealed that under physiological conditions, water molecules replace chloride ligands owing to drug hydration. The subsequent interaction with DNA, led to the bonding of the aqua complexes into the DNA structure with simultaneous loss of the coordinating water and chloride ion. The data analysis reveals that Pt is coordinated by two adjacent guanines giving cis-[Pt(NH3)2{d(GpG)-N7(1),-N7(2)}] upon losing its coordinating water or chloride ligands.
The Henryk Niewodniczanski Institute of Nuclear Physics, PAN, 31-342 Kraków, Poland.
Ewelina
E
Lipiec
Joanna
J
Czapla
Jakub
J
Szlachetko
Yves
Y
Kayser
Wojciech
W
Kwiatek
Bayden
B
Wood
Glen B
GB
Deacon
Jacinto
J
Sá
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D004247:DNA / Q000737:chemistry*; D006860:Hydrogen Bonding; D008958:Models, Molecular; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D017671:Platinum Compounds / Q000737:chemistry* / Q000494:pharmacology*
D000970:Antineoplastic Agents; D017671:Platinum Compounds; D004247:DNA