Cationic porphyrins with large side arm substituents as resonance light scattering ratiometric probes for specific recognition of nucleic acid G-quadruplexes

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.

Chiral Interaction Is a Decisive Factor To Replace d-DNA with l-DNA Aptamers

“…With the addition of l -CatG4 or d -CatG4, the fluorescence at 714 nm greatly increased, accompanied by the decrease in fluorescence at 657 nm. Since neither single- nor double-stranded DNA has been reported to affect the UV–vis absorption and fluorescence signal of TMPipEOPP, − the above-observed optical responses were G-quadruplex-specific and were consistent with previous reports. − These results further demonstrated that both l -CatG4 and d -CatG4 could fold into G-quadruplex structures to bind with porphyrin.…”

“…The above-mentioned experiments demonstrated that the l -DNA-based G-quadruplex could also bind with Hemin. In our previous works, − we have designed a series of highly specific G-quadruplex ligands by introducing bulky side arm substituents into cationic porphyrin derivatives, and found that they could give pronounced optical responses to G-quadruplexes. Here, we used one of our cationic porphyrin compounds (TMPipEOPP) as a G-quadruplex probe − and compared the binding interactions of this porphyrin with l -CatG4 and d -CatG4.…”

Platform- and label-free detection of lead ions in environmental and laboratory samples using G-quadraplex probes by circular dichroism spectroscopy

“…Therefore, PS2.M could be more promising as a detection probes for Pb 2+ in environmental samples, because they caused a suitable absorption signal in CD spectroscopy. The limits of permissible concentration of Pb 2+ in surface water are as follows: 50 ppb for drinking water supply 41 ; 15 ppb for drinking water 42 ; 50-100 ppb for permissible effluent water 43 ; and 200-500 ppm industrial wastewater 36 . In Fig.…”

The Interactions of H2TMPyP, Analogues and Its Metal Complexes with DNA G-Quadruplexes—An Overview

“…Amongst the aromatic macrocycles, porphyrins, such as the cationic H2TMPyP and analogs appear as the most widely tested telomerase inhibitors [32,33,[53][54][55]. Structural attributes such as the presence of an extended heteroaromatic moiety that can interact on the G-quartet surface of a G-quadruplex by π−π stacking, and flexible cationic charged terminal side chains are pointed as essential features for effective ligand binding to a quadruplex and optimal inhibition of telomerase activity [9].…”

“…Other im structural characteristics are the presence of bulky substituents to prevent inter with double-stranded DNA and good solubility in aqueous media. In gener matic/planar molecules such as porphyrins and analogs, especially if positively c Amongst the aromatic macrocycles, porphyrins, such as the cationic H 2 TMPyP and analogs appear as the most widely tested telomerase inhibitors [32,33,[53][54][55].…”