Abstract
The discovery of uncommon DNA structures and speculation about their potential functions in genes has brought attention to specific DNA structure recognition. G-quadruplexes are four-stranded nucleic acid structures formed by G-rich DNA (or RNA) sequences. G-rich sequences with a high potential to form G-quadruplexes have been found in many important genomic regions. Porphyrin derivatives with cationic side arm substituents are important G-quadruplex-binding ligands. For example, 5,10,15,20-Tetrakis(N-methylpyridinium-4-yl)-21H,23H-porphyrin (TMPyP4), interacts strongly with G-quadruplexes, but has poor selectivity for G-quadruplex versus duplex DNA. To increase the G-quadruplex recognition specificity, a new cationic porphyrin derivative, 5,10,15,20-tetra-{4-[2-(1-methyl-1- piperidinyl)ethoxy]phenyl} porphyrin (TMPipEOPP), with large side arm substituents was synthesized, and the interactions between TMPipEOPP and different DNA structures were compared. The results show that G-quadruplexes cause large changes in the UV-Vis absorption and fluorescence spectra of TMPipEOPP, but duplex and single-stranded DNAs do not, indicating that TMPipEOPP can be developed as a highly specific optical probe for discriminating G-quadruplex from duplex and single-stranded DNA. Visual discrimination is also possible. Job plot and Scatchard analysis suggest that a complicated binding interaction occurs between TMPipEOPP and G-quadruplexes. At a low [G-quadruplex]/[TMPipEOPP] ratio, one G-quadruplex binds two TMPipEOPP molecules by end-stacking and outside binding modes. At a high [G-quadruplex]/[TMPipEOPP] ratio, two G-quadruplexes bind to one TMPipEOPP molecule in a sandwich-like end-stacking mode.
Highlights
G-quadruplexes are four-stranded nucleic acid structures formed by G-rich DNA sequences
The twist angles between the four benzene rings and the porphyrin plane are around 60u
For TMPyP4 and TPrPyP4, continuous red shift and hypochromicity are observed with increasing G-quadruplex concentration
Summary
G-quadruplexes are four-stranded nucleic acid structures formed by G-rich DNA (and RNA) sequences. In these structures, four G residues are connected by eight Hoogsteen-type hydrogen bonds to form a G-quartet plane, and several G-quartets stack to form a G-quadruplex [1]. Except for the single-stranded G-rich telomeric 39-overhang, most G-quadruplex-forming sequences are found with their complementary strands. These G-rich sequences can adopt different conformations, folding to G-quadruplex structures, or forming duplex structures by hybridizing with their complementary sequences. A probe that recognizes G-quadruplexes in the presence of duplex and single-stranded DNAs must be developed. To achieve G-quadruplex sensing in vivo, a specific G-quadruplex florescent probe is desirable [9]
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