Interactions of a platinum-modified perylene derivative with the human telomeric G-quadruplex

Lu Rao, Joshua D. Dworkin, William E. Nell, Ulrich Bierbach

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

The interactions of a newly synthesized platinum-modified perylene derivative, compound 7 ([{Pt(dien)}2(μ-4-S,S′)](NO 3)4 (dien = diethylenetriamine, 4 = N,N′-bis(1-(2- aminoethyl)-1,3-dimethylthiourea)-3,4,9,10-perylenetetracarboxylic acid diimide), with the human telomeric repeat were studied using various model oligo(deoxy)ribonucleotides to mimic the polymorphic nature of the telomeric G-quadruplex. UV/visible spectroscopy, CD spectropolarimetry, electrospray mass spectrometry (ES-MS), and isothermal titration calorimetry (ITC) were used to demonstrate that compound 7 selectively recognizes the antiparallel form of the unimolecular telomeric G-quadruplex formed by the sequence d(TTAGGG)4 (dG-24), to which it binds with a 2:1 stoichiometry and nanomolar affinity. Compared with telomeric DNA, the first binding event of compound 7 in titrations with the RNA quadruplex formed by r(UUAGGG)4 (rG-24) is 1 order of magnitude weaker. Compound 7 does not induce the antiparallel G-quadruplex RNA, which invariably exists in a parallel form and dimerizes in solution. On the basis of the cumulative experimental data, two distinct mechanisms are proposed for the recognition of G-quadruplex DNA and RNA by compound 7. Potential biomedical and biochemical applications of the platinum - perylene technology are discussed.

Original languageEnglish (US)
Pages (from-to)13701-13712
Number of pages12
JournalJournal of Physical Chemistry B
Volume115
Issue number46
DOIs
StatePublished - Nov 24 2011
Externally publishedYes

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Perylene
Platinum
RNA
titration
platinum
deoxyribonucleic acid
Derivatives
Titration
DNA
Ribonucleotides
affinity
stoichiometry
mass spectroscopy
heat measurement
interactions
Calorimetry
Stoichiometry
acids
Mass spectrometry
Spectroscopy

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Materials Chemistry
  • Surfaces, Coatings and Films

Cite this

Interactions of a platinum-modified perylene derivative with the human telomeric G-quadruplex. / Rao, Lu; Dworkin, Joshua D.; Nell, William E.; Bierbach, Ulrich.

In: Journal of Physical Chemistry B, Vol. 115, No. 46, 24.11.2011, p. 13701-13712.

Research output: Contribution to journalArticle

Rao, Lu ; Dworkin, Joshua D. ; Nell, William E. ; Bierbach, Ulrich. / Interactions of a platinum-modified perylene derivative with the human telomeric G-quadruplex. In: Journal of Physical Chemistry B. 2011 ; Vol. 115, No. 46. pp. 13701-13712.
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