Investigation of hairpin DNA and chelerythrine interaction by a single bio-nanopore sensing interface.

Chelerythrine (CHE) is one of the potential drugs for cancer treatments. The interaction between hairpin DNA and CHE has been investigated by spectral and mass spectrometry methods. In this paper, the stability of hairpin DNA with different loop bases and its interaction with CHE were explored with a single α-hemolysin (α-HL) nanopore sensing interface. The results showed that the characteristic current pulses not only relate to the loop composition changes of the hairpin DNA, but also provide interaction information between CHE and the hairpin DNA molecules. The dwell time of current pulses for hairpin DNA was significantly increased (hundreds of ms) due to the addition of CHE, and two characteristic current distributions were recognized for the hairpin with T3 and C3 loops. The two characteristic current groups could be ascribed to the hairpin DNA and the ones with CHE. This study indicates that it is possible to study the interaction between single CHE and single hairpin DNA molecules by the single-nanopore sensing interface as an alternative method to conventional spectrometric methods for therapeutic mechanism and drug screening purposes.

Exploring the interaction of G-quadruplex and porphyrin derivative by single protein nanopore sensing interface.

Both human telomere and proto-oncogene c-MYC can form G-quadruplex (G4) with various conformations. Porphyrin derivative (TMPyP4) could stabilize G4, and thus is considered as a potential drug for anticancer therapeutics. In this paper, the translocation behaviors of three typical G4s (telomere basket, telomere hybrid-1 and c-MYC Pu22 parallel) and their interaction with TMPyP4 were investigated with a single protein nanopore sensing interface with the same main electrolyte of 0.5 M tetramethylammonium chloride. As observed by the statistics of the dwell time of the current pulses, in the presence of K+, the parallel G4 is more stable than the hybrid-1 G4, while the basket G4 in the presence of Na+ exhibited shortest duration. The dwell time of all of the G4s increased as the result of interaction with TMPyP4, indicating an obvious stabilizing effect. This study demonstrated that the single nanopore sensing interface not only reveal the stability of various G4 conformations at a single-molecule level, but also provide the interaction information of a ligand, which could be useful in the drug design.