Interactions between meso-tetrakis(4-(N-methylpyridiumyl))porphyrin TMPyP4 and DNA G-quadruplex of telomeric repeated sequence TTAGGG

Abstract

The binding properties between meso-tetrakis(4-(N-methylpyridiumyl))porphyrin (TMPyP4) and the parallel DNA G-quadruplex (G4) of telomeric repeated sequence 5ƍ-TTAGGG-3ƍ have been characterized by means of circular dichroism, steady-state absorption, steady-state fluorescence and picosecond time-resolved fluorescence spectroscopies. The binding constant and the saturated binding number were determined as 1.29×10 6 (mol/L) 1 and 3, respectively, according to steady-state absorption spectroscopy. Based on the findings by the use of time-resolved fluorescence spectroscopic technique, it is deduced that TMPyP4 binds to a DNA G-quadruplex with both the thread-intercalating and end-stacking modes and at the saturated binding state, one TMPyP4 molecule intercalates into the intervals of G-tetrads while the other two stack to the ends of the DNA G-quadruplex.

A Spherical Nucleic Acid Platform Based on Self-Assembled DNA Biopolymer for High-Performance Cancer Therapy

“…Aptamer AS1411 characterized by the G-quadruplex structure was a stable candidate for carrying a quadruplex ligand, such as 5,10,15,20-tetrakis(4- N -methyl­pyridiniumyl)­porphyrin (TMPyP4). TMPyP4 is a broadly used photodynamic therapy (PDT) reagent which has been identified as an effective G-quadruplex DNA-binding ligand. − However, TMPyP4 has poor selectivity and is toxic to some normal cell lines, especially normal fibroblasts and epithelium, when exposed to light . Therefore, in recent studies, targeted delivery, such as aptamer, has been successfully used to increase the accumulation at the target site and to prevent toxicity to the neighboring tissues. , Compared to this reported work, a new AS1411/MNP-SNA platform was proposed in our design, and multiple copies of AS1411 could be embedded in the long DNA biopolymer on the surface of the nanoparticle.…”

Fluorescent Probes for G‐Quadruplex Structures

“…[147,150] TmPyP4 is modestly fluorescent in water (F = 0.04), [151] but is quenched upon G-quadruplex binding, by photon-induced electron transfer from guanine residues. [148,152] TMPyP4 can, however, exhibit a twofold higher quantum yield (F = 0.08) when it is bound to AT-rich duplex DNA. [149,152] This photophysical selectivity for duplex DNA can be partially overcome by monitoring energy transfer reactions from G-quadruplexes to TMPyP4 that result from photoexcitation of the DNA at 260 nm.…”

“…[148,152] TMPyP4 can, however, exhibit a twofold higher quantum yield (F = 0.08) when it is bound to AT-rich duplex DNA. [149,152] This photophysical selectivity for duplex DNA can be partially overcome by monitoring energy transfer reactions from G-quadruplexes to TMPyP4 that result from photoexcitation of the DNA at 260 nm. [124] At the present time, however, this type of approach is not compatible with cellular imaging because of the practical limitations of photoexcitation and autofluoresence in the UV range.…”

Self‐Assembly of a Bifunctional DNA Carrier for Drug Delivery

“…Stabilization of the G‐quadruplex structure is achieved by such cations as K + and Na + . More important to the present report, the photosensitizer 5,10,15,20‐tetrakis‐(1‐methyl‐4‐pyridyl)‐21 H ,23 H ‐porphine (TMPyP4) tends to intercalate into G‐quadruplex structures,19–22 and, as such, it can be delivered to a target cell by a high‐affinity aptamer. When activated by light of a specific wavelength, the photosensitizer transfers the light energy to molecular oxygen to generate reactive oxygen species (ROS), which mediate cellular toxicity 23.…”