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

The interactions of a newly synthesized platinum-modified perylene derivative, compound 7 ([{Pt(dien)}(2)(micro-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.