Studies on the interaction mechanism of pyrene derivatives with human tumor-related DNA

Abstract

Pyrene derivatives can be carcinogenic, teratogenic and mutagenic, thus having the potential to cause malignant diseases. In this work, the interactions of two selected pyrene derivatives (1-OHP and 1-PBO) and human tumor-related DNA (p53 DNA and C-myc DNA) are investigated by spectroscopic and non-native polyacrylamide gel electrophoresis (PAGE) methods. Using fluorescence spectrometry and circular dichroism (CD), DNA interactions of pyrene derivatives are confirmed to occur mainly via the groove binding mode supported by the intercalation into the base pairs of DNA. There is an obvious binding order of pyrene derivatives to the targeted DNA, 1-OHP > 1-PBO. The binding constants of 1-OHP are 1.16 × 10(6) L × mol(-1) and 4.04 × 10(5) L × mol(-1) for p53 DNA and C-myc DNA, respectively, while that of 1-PBO are only 2.04 × 10(3) L × mol(-1) and 1.39 × 10(3) L × mol(-1) for p53 DNA and C-myc DNA, respectively. Besides, the binding of pyrene derivatives to p53 DNA is stronger than that for C-myc DNA. CD and PAGE results indicate that the binding of pyrene derivatives can affect the helical structures of DNA and further induce the formation of double-chain antiparallel G-quadruplex DNA of hybrid G-rich sequences.

Figure 1

Structures of pyrene derivatives.

Figure 2

Fluorescence spectra of the pyrenederivatives solution (1 μmol/L) with the addition of p53 DNA (0-20 μmol/L). (A) 1-OHP and (B) 1-PBO. The arrows show the fluorescence changes at peak wavelength with the DNA concentration increased.

Figure 3

The Stern-Volmer plots of the fluorescence quenching of pyrene derivatives by C-myc DNA at 298 K and 310 K (the concentrations of pyrene derivatives are 1 μmol/L, pH = 7.4). (A) 1-OHP and (B) 1-PBO.

Figure 4

Quenching extents of pyrene derivatives solutions (1 μmol/L) with the addition of KI (0–20 μmol/L) in the absence and presence of C-myc DNA (10 μmol/L). (A) 1-OHP and (B) 1-PBO.

Figure 5

CD and ICD spectra of DNA solutions (5 μmol/L) with the addition of 1-PBO (0–20 μmol/L). (A) CDspectra of p53 DNA; (B) CDspectra of C-myc DNA; (C) ICDspectra of p53 DNA and (D) ICDspectra of C-myc DNA.

Figure 6

Transient fluorescence spectra of pyrene derivatives (1 μmol/L) in the absence and presence of DNA (10 μmol/L).(A) 1-OHP and (B) 1-PBO.

Figure 7

PAGE image of p53 DNA with the addition of 1-OHP solution in different molar ratio. (Lane M): DNA marker, (Lane 1–5): the molar ratio of DNA and 1-OHP is 1:0, 1:1, 1:5, 1:10 and 1:20, respectively.