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Metallodrug–protein interaction probed by synchrotron terahertz and neutron scattering spectroscopy

DOI: 10.1016/j.bpj.2021.06.012 DOI Help

Authors: L. A. E. Batista De Carvalho (University of Coimbra) , A. P. Mamede (University of Coimbra) , A. L. M. Batista De Carvalho (University of Coimbra) , J. Marques (University of Coimbra) , G. Cinque (Diamond Light Source) , S. Rudic (ISIS Facility) , M. P. M. Marques (University of Coimbra)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Biophysical Journal

State: Published (Approved)
Published: June 2021
Diamond Proposal Number(s): 21620

Abstract: The present experimental work applied coherent synchrotron-radiation THz spectroscopy and inelastic neutron scattering to address two processes directly associated with the mode of action of metal-based anticancer agents, that can severely undermine chemotherapeutic treatment: drug binding to human serum albumin, occurring during intravenous drug transport, and intracellular coordination to thiol-containing biomolecules (such as metallothioneins), associated with acquired drug resistance. Cisplatin and two dinuclear Pt- and Pd-polyamine agents developed by this research group, which have yielded promising results towards some types of human cancers, were investigated. Complementary SR-THz and INS data revealed protein metallation, through S- and N-donor ligands from cysteine, methionine and histidine residues. A clear impact of the Pt- and Pd-agents was evidenced, drug-binding to albumin and metallothionein having been responsible for significant changes in the overall protein conformation, as well as for an increased flexibility and possible aggregation.

Subject Areas: Medicine, Chemistry, Biology and Bio-materials

Instruments: B22-Multimode InfraRed imaging And Microspectroscopy

Other Facilities: TOSCA (50-53) at ISIS

Added On: 05/07/2021 09:19

Discipline Tags:

Organic Chemistry Life Sciences & Biotech Biophysics Health & Wellbeing Cancer Drug Discovery Non-Communicable Diseases Chemistry

Technical Tags:

Spectroscopy Infrared Spectroscopy Synchtron-based Fourier Transform Infrared Spectroscopy (SR-FTIR)