Comparative thermodynamics for monomer and dimer sequence-dependent binding of a heterocyclic dication in the DNA minor groove.
Phenylamidine cationic groups linked by a furan ring (furamidine) and related symmetric diamidine compounds bind as monomers in the minor groove of AT sequences of DNA. DB293, an unsymmetric derivative with one of the phenyl rings of furamidine replaced with a benzimidazole, can bind to AT sequences as a monomer but binds more strongly to GC-containing minor-groove DNA sites as a stacked dimer. The dimer-binding mode has high affinity, is highly cooperative and sequence selective. In order to develop a better understanding of the correlation between structural and thermodynamic aspects of DNA molecular recognition, DB293 was used as a model to compare the binding of minor-groove agents with AT and mixed sequence DNA sites. Isothermal titration calorimetry and surface plasmon resonance results clearly show that the binding of DB293 and other related compounds into the minor groove of AT sequences is largely entropy-driven while the binding of DB293 as a dimer into the minor groove of GC-containing sequences is largely enthalpy-driven. At 25 degrees C, for example, the AT binding has DeltaG degrees, DeltaH degrees and TDeltaS degrees values of -9.6, -3.6 and 6.0 kcal/mol while the values for dimer binding to a GC-containing site are -9.0, -10.9 and -1.9 kcal/mol (per mol of bound compound), respectively. These results show that the thermodynamic components for binding of compounds of this type to DNA are very dependent on the structure, solvation and sequence of the DNA binding site.
Wang
Lei
L
Department of Chemistry, Georgia State University, Atlanta, GA 30303, USA.
Kumar
Arvind
A
Boykin
David W
DW
Bailly
Christian
C
Wilson
W David
WD
D001483:Base Sequence; D001550:Benzamidines / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D002151:Calorimetry; D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D006860:Hydrogen Bonding; D008024:Ligands; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D012997:Solvents; D055672:Static Electricity; D013379:Substrate Specificity; D020349:Surface Plasmon Resonance; D013696:Temperature; D013816:Thermodynamics
D001550:Benzamidines; D008024:Ligands; D012997:Solvents; C033286:furamidine; D004247:DNA