Interaction of human telomeric DNA with N- methyl mesoporphyrin IX

Abstract

The remarkable selectivity of N-methyl mesoporphyrin IX (NMM) for G-quadruplexes (GQs) is long known, however its ability to stabilize and bind GQs has not been investigated in detail. Through the use of circular dichroism, UV-visible spectroscopy and fluorescence resonance energy transfer (FRET) melting assay we have shown that NMM stabilizes human telomeric DNA dAG3(TTAG3)3 (Tel22) and is selective for its parallel conformation to which it binds in 1:1 stoichiometry with a binding constant of ∼1.0 × 105 M−1. NMM does not interact with an antiparallel conformation of Tel22 in sodium buffer and is the second example in the literature, after TOxaPy, of a ligand with an excellent selectivity for a specific GQ structure. NMM's stabilizing ability toward predominantly parallel GQ conformation is universal: it stabilizes a variety of biologically relevant G-rich sequences including telomeres and oncogene promoters. The N-methyl group is integral for selectivity and stabilization, as the unmethylated analogue, mesoporphyrin IX, does not stabilize GQ DNA in FRET melting assays. Finally, NMM induces the isomerization of Tel22 into a structure with increased parallel component in K+ but not in Na+ buffer. The ability of NMM to cause structural rearrangement and efficient stabilization of Tel22 may bear biological significance.

An RNA-binding Protein, Lin28, Recognizes and Remodels G-quartets in the MicroRNAs (miRNAs) and mRNAs It Regulates

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A high-throughput fluorescent indicator displacement assay and principal component/cluster data analysis for determination of ligand-nucleic acid structural selectivity

“…These compounds have higher affinity for GC-rich DNA structures (25). Cluster 3 (green) contains NMM580 and methylene blue that are selective for G4s (21,25,86,87). Cluster 4 (blue) includes the remaining compounds that have low selectivity.…”

A Label-free “Turn-on” Fluorescence Method for Detecting Mercury Ion in Aqueous Solution Based on N-Methyl Mesoporphyrin IX (NMM)/G-quadruplex DNA

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