TY - JOUR
T1 - Structural characterization of a rigidified threading bisintercalator
AU - Chu, Yongjun
AU - Sorey, Steven
AU - Hoffman, David W.
AU - Iverson, Brent L.
PY - 2007/2/7
Y1 - 2007/2/7
N2 - 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.
AB - 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.
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U2 - 10.1021/ja066480x
DO - 10.1021/ja066480x
M3 - Article
C2 - 17263414
AN - SCOPUS:33846828661
SN - 0002-7863
VL - 129
SP - 1304
EP - 1311
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 5
ER -