Binding Studies of G-Quadruplex DNA and Porphyrins: Cu(T4) vs Sterically Friendly Cu(tD4)

作者：Gaier Abby J; McMillin David R^*

来源：Inorganic Chemistry, 2015, 54(9): 4504-4511.

DOI：10.1021/acs.inorgchem.5b00340

This investigation explores binding interactions involving G-quadruplex DNA and two copper(II)-containing porphyrins (5,10,15,20-tetra(N-methylpyridinium-4-y1)porphyrinato)copper(II) and the sterically friendlier analogue (trans-5,15-di(N-methylpyridinium-4-yl-porphyrinato) copper(II), or Cu(T4) and Cu(tD4), respectively. The study incorporates five different DNA sequences that support the formation of unimolecular and bimolecular G-quadruplex hosts capable of exhibiting at least nine different structures in toto. Absorbance and emission results establish that G-quadruplex DNA is more adept at sequestering Cu(tD4) compared with the bulkier Cu(T4) ligand, even though the predominant mode of uptake is by end-capping, irrespective of the porphyrin or DNA sequence employed. One of the more impressive observations is that the emission intensities exhibited by Cu(tD4) bound to G-quadruplex DNA are many-fold higher than corresponding signals obtained with single- or double-stranded DNA hosts. With human sequence DNA the Cu(tD4) System is also unusual in that it preferentially binds to structures containing antiparallel strands. Refining the binding properties of porphyrin ligands is of interest because work from many laboratories has established that stabilizing G-quadruplex structure is an effective way to inhibit telomerase, a key enzyme involved in the immortalization of most types of cancer cells.

• 出版日期2015-5-4