6H5R

Structure of the complex of a human telomeric DNA with bis(1-butyl-3-methyl-imidazole-2-ylidene) gold(I)

Summary for 6H5R

• Entry DOI: 10.2210/pdb6h5r/pdb
• Descriptor: Human Telomeric DNA, POTASSIUM ION, STRONTIUM ION, ... (5 entities in total)
• Functional Keywords: drug-dna complex, g quadruplex, dna
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 9651.25

Authors

Bazzicalupi, C.,Gratteri, P.,Papi, F. (deposition date: 2018-07-25, release date: 2019-01-30, Last modification date: 2024-01-17)

Primary citation

Guarra, F.,Marzo, T.,Ferraroni, M.,Papi, F.,Bazzicalupi, C.,Gratteri, P.,Pescitelli, G.,Messori, L.,Biver, T.,Gabbiani, C.
Interaction of a gold(i) dicarbene anticancer drug with human telomeric DNA G-quadruplex: solution and computationally aided X-ray diffraction analysis.
Dalton Trans, 47:16132-16138, 2018

PubMed Abstract: The bis carbene gold(i) complex [Au(1-butyl-3-methyl-2-ylidene)2]PF6, ([Au(NHC)2]PF6 hereafter), holds remarkable interest as a perspective anticancer agent. The compound is stable under physiological like conditions: its original structure is retained even in the presence of excess glutathione (GSH). Previous studies revealed its high cytotoxicity in vitro that correlates with the impairment of crucial metabolic and enzymatic cellular processes (Magherini et al., Oncotarget, 2018, 9, 28042). Here, the interaction of [Au(NHC)2]PF6 with the human telomeric DNA G-quadruplex Tel23 has been investigated in solution by means of high resolution mass spectrometry. ESI MS experiments well document the formation of stable 1 : 1 adducts between the biscarbene gold complex - in its intact form - and the DNA G-quadruplex Tel23. Next, through independent biophysical methods, we show that [Au(NHC)2]PF6 binding does not significantly affect the G quadruplex melting temperature nor its conformation. The crystal structure for the [Au(NHC)2]+/Tel24 adduct was eventually determined by a joint X-ray diffraction and in silico simulation approach. Through the careful integration of solution and solid-state data, a quite clear picture emerges for the interaction of this gold complex with the Tel23 G-quadruplex.

PubMed: 30378627
DOI: 10.1039/c8dt03607a

Experimental method

X-RAY DIFFRACTION (2 Å)