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Author Spotlight: Characterizing DNA G-Quadruplex by Bis-3-Chloropiperidine Based Chemical Mapping

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Multicolorfully probing intramolecular G-Quadruplex tandem interface.

Yali Yu¹, Qingqing Zhang¹, Yifan Fei¹

¹Key Laboratory of the Ministry of Education for Advanced Catalysis Materials, Institute of Physical Chemistry, College of Chemistry and Life Sciences, Zhejiang Normal University, Jinhua, 321004, Zhejiang, China.

Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy

|November 1, 2019

Summary

This summary is machine-generated.

A novel porphyrin derivative, OH₂PP, distinguishes between stacked and unstacked G-quadruplex interfaces using multicolor fluorescence. This method offers sensitive detection of G-quadruplex multimers, crucial for understanding their bioactivity.

Keywords:

DNA G-quadruplex Multicolor fluorescence Porphyrin Selectivity Tandem interface

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Area of Science:

Biochemistry
Molecular Biology
Chemical Biology

Background:

Guanine-rich oligonucleotides can form G-quadruplex (G4) structures.
Tandem G4 arrangements create internal interfaces (inG4-G4) that can be stacked (s-inG4-G4) or unstacked (us-inG4-G4).
G4 interface states are biologically significant, necessitating methods for their differentiation.

Purpose of the Study:

To develop a multicolor fluorescence method for distinguishing between s-inG4-G4 and us-inG4-G4 interfaces.
To identify a fluorophore capable of specific, wavelength-dependent recognition of G4 interface states.

Main Methods:

Synthesis and characterization of a porphyrin with four dihydroxyphenyl substituents (OH₂PP).
Spectroscopic analysis (excitation and emission shifts) of OH₂PP interaction with G4 monomers, s-inG4-G4 dimers, and us-inG4-G4 dimers.
Investigation of OH₂PP binding modes (stoichiometry) and dependence on linker length between G4 units.

Main Results:

OH₂PP exhibits distinct multicolor fluorescence responses to s-inG4-G4 and us-inG4-G4 interfaces.
Significant red shifts in OH₂PP spectra were observed for s-inG4-G4 dimers compared to us-inG4-G4 dimers and G4 monomers.
OH₂PP binds in a 1:1 mode with s-inG4-G4 dimers and a 2:1 mode with us-inG4-G4 dimers.
The limit of detection for s-inG4-G4 structures was in the tens of nanomolar range.
Porphyrin macrocycle deformation within the s-inG4-G4 interface likely causes the observed spectral changes.

Conclusions:

OH₂PP is a sensitive and specific fluorophore for differentiating between stacked and unstacked G4 interfaces.
The findings enable multicolor fluorescent recognition of G4 multimers based on their interface conformation.
This work provides a valuable tool for studying the bioactivity of G4 structures.