Investigation of TMPYP4 porphyrin interaction with AS1411 aptamer using spectroscopic methods

Spectral properties and thermal stability of AS1411 G-quadruplex AS1411 is an anticancer four-stranded deoxyoligonucleotide with high affinity and specificity to a putative surface biomarker, nucleolin, which is an overexpressed protein on numerous cancer cells. AS1411 has valuable functional potential for the targeted delivery of nanoparticles, oligonucleotides, peptides and small drug molecules to cancer cells. Considering that understanding interaction of drug with target molecule is important and necessary for pharmaceutical studies, in the present study, the interaction of a porphyrin photosensitizer called TMPYP4 was evaluated with aptamer AS1411. Absorption and fluorescence spectroscopy and circular dichroism technique were used to identify how and where TMPYP4 binds to AS1411 and the resulting structural changes. The results showed that binding of the porphyrin to AS1411 caused 13 nm red shift and 56% hypochromicity in the absorption spectrum; in addition, due to this binding, the emission spectrum of porphyrin is changed and its emission intensity is reduced. The results of structural studies showed that the binding of TMPYP4 does not significantly change the shape of the AS1411 circular dichroism spectrum, but at high concentrations leads to an intense decrease in the intensity of the spectrum. These changes in the spectra indicate that TMPYP4 binds to the aptamer through intercalation between tetrad planes and end-staking and causes to opening of the aptamer structure. As a conclusion, it can be proposed that AS1411 aptamer has appropriate potential for delivery of porphyrin compounds and their photosensitizer types and can be used in photodynamic therapy of cancer cells.