Abstract
Specific G-quadruplex-probing is crucial for both biological sciences and biosensing applications. Most reported probes are focused on fluorescent or colorimetric recognition of G-quadruplexes. Herein, for the first time, we reported a new specific G-quadruplex-probing technique—resonance light scattering (RLS)-based ratiometric recognition. To achieve the RLS probing of G-quadruplexes in the important physiological pH range of 7.4-6.0, four water soluble cationic porphyrin derivatives, including an unreported octa-cationic porphyrin, with large side arm substituents were synthesized and developed as RLS probes. These RLS probes were demonstrated to work well for ratiometric recognition of G-quadruplexes with high specificity against single- and double-stranded DNAs, including long double-stranded ones. The working mechanism was speculated to be based on the RLS signal changes caused by porphyrin protonation that was promoted by the end-stacking of porphyrins on G-quadruplexes. This work adds an important member in G-quadruplex probe family, thus providing a useful tool for studies on G-quadruplex-related events concerning G-quadruplex formation, destruction and changes in size, shape and aggregation. As a proof-of-concept example of applications, the RLS probes were demonstrated to work well for label-free and sequence-specific sensing of microRNA. This work also provides a simple and useful way for the preparation of cationic porphyrins with high charges.
Highlights
OMHEPzEOPP was well-characterized with 1H-nuclear magnetic resonance (1H-Nuclear magnetic resonance (NMR)) spectroscopy and 13C-NMR spectroscopy, and the two intermediates of TBrEOPP, THEPzEOPP were all well-characterized with 1H-NMR spectroscopy and mass spectroscopy (MS) to confirm the product structure and assure the product purity
By comparing the 1H-NMR spectra of THEPzEOPP and OMHEPzEOPP, it was found that OMHEPzEOPP showed a new single peak at 3.59 ppm which contained 24 hydrogens, indicating that the nitrogen atoms on the four piperazine rings were successfully linked by methyl groups
Previous studies from our and other groups demonstrated that the presence of positive charges in porphyrin derivatives could promote their binding with DNA through electrostatic interaction [40,41,42,43,45,46]
Summary
G-quadruplexes are noncanonical nucleic acid secondary structure formed by guanine (G)-rich DNAs or RNAs.Since genomic sequences with G-quadruplex-forming potential are widely found in many important regions of human genome and increasing evidences reveal that Gquadruplex formation in these regions is closely related with some crucial biological functions [1,2,3,4,5,6,7,8], G-quadruplexes represent promising targets for development of new anticancer drugs [9,10,11,12,13,14,15,16]. No matter for biological sciences or biosensing applications, searching for an excellent G-quadruplex probe with high G-quadruplex recognition specificity against other nucleic acid structures is a necessary prerequisite. Through the efforts of many researchers, a large number of G-quadruplex probes showing excellent G-quadruplex recognition performance have been reported [25,26,27,28,29,30,31,32,33,34]. Most of these probes are focused on the fluorescent recognition of G-quadruplexes, and the one that can achieve G-quadruplex-probing via resonance light scattering (RLS) signals has never been reported
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