Conformational rearrangements of G-quadruplex topology promoted by Cu(II) 12-MCCu(II)PyrAcHA-4 metallacrown.

Abstract:

:Cu(II) 12-MCCu(II)PyrAcHA-4 metallacrown was studied by several spectroscopic techniques as an interacting ligand with G-quadruplex DNA structures. Investigations were performed on oligonucleotides bearing human telomeric and protooncogenic c-myc sequences in buffered solution mimicking ionic conditions in cellular environment. The planar square-based Cu(II) 12-MC-4 metallacrown interacts with GQ via an end-stacking mode with 1:1 stoichiometry. Circular dichroism (CD) titration revealed capability of this metallacrown to induce transformation of the GQ hybrid topology into the parallel form. Thermal melting experiment indicated higher thermal stability of both antiparallel (ΔTm = +15 °C) and parallel (ΔTm = ≥27 °C) G-quadruplexes in the presence of Cu (II) 12-MC-4. Indirect GQ FID assay let to determine high binding affinity of the Cu(II) 12-MC-4 to antiparallel 22Htel/Na+ GQ (KMC = 3.9 (±0.4) x 106 M-1). Comparing with lower binding constants previously reported for Ln (III) 15-MC-5 and Sm (III) 12-MC-4, one can conclude that the square planar geometry and the positive charge of metallacrown play an important role in MC/GQ interactions.

journal_name

Int J Biol Macromol

authors

Rajczak E,Juskowiak B

doi

10.1016/j.ijbiomac.2019.11.163

subject

Has Abstract

pub_date

2020-08-01 00:00:00

pages

1258-1269

eissn

0141-8130

issn

1879-0003

pii

S0141-8130(19)37555-5

journal_volume

156

pub_type

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