Anticancer Drug Impact on DNA – A Study by Neutron Spectrocopy, Synchrotron-based FTIR and EXAFS
Anticancer Drug Impact on DNA – A Study by Neutron Spectrocopy, Synchrotron-based FTIR and EXAFS
ABSTRACT A complementary structural and dynamical information on drug-DNA interplay has been achieved at a molecular level, for Pt/Pd-drugs, allowing a better understanding of their pharmacodynamic profile. The interaction of two cisplatin-like dinuclear Pt(II) and Pd(II) complexes with DNA was studied through a multidisciplinary experimental approach, using quasi-elastic neutron scattering (QENS) techniques coupled to synchrotron-based extended X-ray absorption fine structure (SR-EXAFS) and Fourier-Transform Infrared Spectroscopy-Attenuated Total Reflectance (SR-FTIR-ATR). The drug impact on DNA’s dynamical profile, via its hydration layer, was provided by QENS, a drug-triggered enhanced mobility having been revealed. Additionally, an onset of anharmonicity was detected for dehydrated DNA, at room temperature. Far- and mid-infrared measurements allowed the first simultaneous detection of the drugs and its primary pharmacological target, as well as the drug-prompted changes in DNA’s conformation that mediate cytotoxicity in DNA extracted from drug-exposed human triple negative breast cancer cells (MDA-MB-231), a low prognosis type of cancer. The local environment of the absorbing Pd(II) and Pt(II) centers in the drugs’ adducts with adenine, guanine and glutathione was attained by EXAFS.
Frogley Mark、Gianolio Diego、Marques Maria P.M.、de Carvalho Ana L.M. Batista、Doherty James、Cinque Gianfelice、Dopplapudi Asha、Gardner Peter、de Carvalho Lu¨as A.E. Batista、Mamede Adriana P.、Sakai Victoria Garcia
Diamond Light Source, Harwell Science and Innovation CampusDiamond Light Source, Harwell Science and Innovation CampusQu¨amica-F¨asica Molecular?±, Department of Chemistry, University of Coimbra||Department of Life Sciences, University of CoimbraQu¨amica-F¨asica Molecular?±, Department of Chemistry, University of CoimbraDiamond Light Source, Harwell Science and Innovation Campus||Manchester Institute of Biotechnology, University of ManchesterDiamond Light Source, Harwell Science and Innovation CampusISIS Facility, STFC Rutherford Appleton LaboratoryManchester Institute of Biotechnology, University of ManchesterQu¨amica-F¨asica Molecular?±, Department of Chemistry, University of CoimbraQu¨amica-F¨asica Molecular?±, Department of Chemistry, University of CoimbraISIS Facility, STFC Rutherford Appleton Laboratory
医学研究方法基础医学药学
Pt and Pd anticancer drugsDNAhuman triple negative breast cancerQENSsynchrotron-based FTIRsynchrotron-based EXAFS
Frogley Mark,Gianolio Diego,Marques Maria P.M.,de Carvalho Ana L.M. Batista,Doherty James,Cinque Gianfelice,Dopplapudi Asha,Gardner Peter,de Carvalho Lu¨as A.E. Batista,Mamede Adriana P.,Sakai Victoria Garcia.Anticancer Drug Impact on DNA – A Study by Neutron Spectrocopy, Synchrotron-based FTIR and EXAFS[EB/OL].(2025-03-28)[2025-06-22].https://www.biorxiv.org/content/10.1101/398826.点此复制
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