Structural characterization of a rigidified threading bisintercalator.
NMR spectroscopy was used to explore the sequence-specific interaction of DNA with a new threading bisintercalator (C1) consisting of two intercalating 1,4,5,8-naphthalenetetracarboxylic diimide (NDI) units connected by a rigid, tricyclic spiro linker. A structural model of C1 complexed to d(CGGTACCG)(2) was calculated using distance constraints obtained from solution NMR data. The model was also supported by the results from residual dipolar coupling (RDC) measurements obtained using Pf1-phage as a cosolvent. According to the model, the central cyclohexane ring of the linker connecting the two NDI units lies flat in the minor groove of DNA. Linker length, hydrogen bonding, steric, and hydrophobic factors all appear to contribute to the observed sequence specificity of binding. These results serve to illustrate the versatility of threading polyintercalation given that, in a previous study, a ligand consisiting of two NDI units joined by a flexible peptide linker was shown to bind sequence specifically within the major groove of this same sequence of DNA.
Chu
Yongjun
Y
Department of Chemistry and Biochemistry, The University of Texas at Austin, Austin, Texas 78712, USA.
Sorey
Steven
S
Hoffman
David W
DW
Iverson
Brent L
BL
D020029:Base Pairing; D001483:Base Sequence / Q000235:genetics; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D007094:Imides / Q000737:chemistry*; D007364:Intercalating Agents / Q000737:chemistry*; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D009281:Naphthalenes / Q000737:chemistry*; D009690:Nucleic Acid Conformation
C429685:1,4,5,8-naphthalenetetracarboxylic diimide; D007094:Imides; D007364:Intercalating Agents; D008024:Ligands; D009281:Naphthalenes; D004247:DNA