Structure-specific recognition of quadruplex DNA by organic cations: influence of shape, substituents and charge.
Combining structure-specific recognition of nucleic acids with limited sequence reading is a promising method to reduce the size of the recognition unit required to achieve the necessary selectivity and binding affinity to control function. It has been demonstrated recently that G-quadruplex DNA structures can be targeted by organic cations in a structure-specific manner. Structural targets of quadruplexes include the planar end surfaces of the G-tetrad stacked columns and four grooves. These provide different geometries and functional groups relative to duplex DNA. We have used surface plasmon resonance and isothermal titration calorimetry to show that binding affinity and selectivity of a series of quadruplex end-stacking molecules to human telomeric DNA are sensitive to compound shape as well as substituent type and position. ITC results indicate that binding is largely enthalpy driven. Circular dichroism was also used to identify a group of structurally related compounds that selectively target quadruplex grooves.
White
Elizabeth W
EW
Department of Chemistry, Georgia State University, Atlanta, GA 30303, USA.
Tanious
Farial
F
Ismail
Mohamed A
MA
Reszka
Anthony P
AP
Neidle
Stephen
S
Boykin
David W
DW
Wilson
W David
WD
D002151:Calorimetry; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry*; D054856:G-Quadruplexes; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D009930:Organic Chemicals / Q000737:chemistry; D020349:Surface Plasmon Resonance
D009930:Organic Chemicals; D004247:DNA