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

• Published in: Nucleic acids research 2019-04, Vol.47 (6), p.2727-2738
• Main Authors: Zhang, Li-Ming, Cui, Yun-Xi, Zhu, Li-Na, Chu, Jun-Qing, Kong, De-Ming
• Format: Article
• Language: English
• Subjects: Binding Sites; Biosensing Techniques - methods; Calorimetry - methods; Cations - chemical synthesis; Cations - chemistry; Cations - metabolism; Chemical Biology and Nucleic Acid Chemistry; Circular Dichroism; G-Quadruplexes; Light; Molecular Probes - chemical synthesis; Molecular Probes - chemistry; Molecular Probes - metabolism; Nuclear Magnetic Resonance, Biomolecular - methods; Nucleic Acids - analysis; Nucleic Acids - isolation & purification; Nucleic Acids - metabolism; Optical Imaging - methods; Porphyrins - chemical synthesis; Porphyrins - chemistry; Porphyrins - metabolism; Protein Structure, Secondary; Scattering, Radiation
• ISSN: 0305-1048; 1362-4962
• DOI: 10.1093/nar/gkz064

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.