Asymmetry and dynamics in bis-intercalated DNA.
The bis-intercalator ditercalinium (NSC 366241), composed of two 7 H-pyridocarbazoles linked by a bis(ethylpiperidinium), binds to DNA with a binding constant greater than 10(7) M-1. One distinctive aspect of the 3-D X-ray structure of a DNA-ditercalinium complex is its asymmetry. We propose here that the activity of ditercalinium may be related to structural polymorphism and dynamic conversion between conformers. It was previously reported that activity is closely related to linker composition. Activity increases with increasing conformational restraints of the linker. We suggest these conformational restraints can lead to asymmetry in DNA complexes and that this asymmetry results directly in structural polymorphism. Using the Cambridge Structural Database (CSD) as a source of information about chemical fragments that are analogous to the linker of ditercalinium, we have explored the conformational space available to ditercalinium. The results indicate that the linker is highly constrained and that the DNA complex is intrinsically asymmetric. We propose a reasonable mechanism of ring reversal that is consistent with the conformations of analogous fragments within the CSD.
Peek
M E
ME
School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta 30332-0400, USA.
Lipscomb
L A
LA
Haseltine
J
J
Gao
Q
Q
Roques
B P
BP
Garbay-Jaureguiberry
C
C
Williams
L D
LD
D000970:Antineoplastic Agents / Q000737:chemistry*; D002227:Carbazoles / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D016208:Databases, Factual; D007364:Intercalating Agents / Q000737:chemistry*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D002227:Carbazoles; D007364:Intercalating Agents; D004247:DNA; C042804:ditercalinium