A thermodynamic and structural analysis of DNA minor-groove complex formation 1 1Edited by I. Tinoco

Mazur, Suzann; Fa, Tanious; Ding, Desheng; Kumar, Arvind; Dw, Boykin; Simpson, I.J.; Neidle, Stephen; Wilson, W. David

doi:10.1006/jmbi.2000.3869

Cited by 128 publications

(149 citation statements)

References 50 publications

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“…The ΔC p for the alternating polymer is close to the value observed for DB75 binding to the -AATT-site in a duplex oligomer [47]. The value is also close to the predicted value of ΔC p based on changes in solvent accessible surface area on binding and calculated from an equation from Chaires and coworkers [36] based on small molecule-DNA experiments.…”

Section: Discussionsupporting

confidence: 81%

“…At 25 °C, for example, the nonalternating sequence has ΔH = +3.1 kcal/mole while the alternating sequence binds with an exothermic enthalpy of −4.5 kcal/mole. At the same temperature ΔH = −2.2 kcal/mole for the AATT oligomer [47]. The three AT sequences have very similar binding Gibbs energies but they obtain the similar affinities with a large variation in the underlying thermodynamics of binding.…”

Section: Discussionmentioning

confidence: 95%

“…Given the increasing importance of diamidines as DNA-targeted therapeutics and biotechnology reagents, it is important to establish the variations in thermodynamic quantities that characterize their interactions at different sequence AT binding sites. Since a thermodynamic analysis of DB75 has been previously conducted with d (CGCGAATTCGCG) 2 [47] that compound has been used with the alternating and nonalternating DNA sequences of different length in the research reported here to probe the sequence dependent thermodynamics of binding. Since extended AT sequences in parasitic mitochondrial kinetoplast DNA have been shown to be the biological target of diamidines [22], these studies are part of the essential information needed for detailed understanding of the therapeutic activity of DB75 and for design of new drugs.…”

Section: Discussionmentioning

confidence: 99%

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Sequence and length dependent thermodynamic differences in heterocyclic diamidine interactions at AT base pairs in the DNA minor groove

Liu

Kumar

Boykin

et al. 2007

Biophysical Chemistry

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With the goal of developing a better understanding of the antiparasitic biological action of DB75, we have evaluated its interaction with duplex alternating and nonalternating sequence AT polymers and oligomers. These DNAs provide an important pair of sequences in a detailed thermodynamic analysis of variations in interaction of DB75 with AT sites. The results for DB75 binding to the alternating and nonalternating AT sequences are quite different at the fundamental thermodynamic level. Although the Gibbs energies are similar, the enthalpies for DB75 binding with poly(dA)·poly (dT) and poly(dA-dT)·poly(dA-dT) are +3.1 and −4.5 kcal/mole, respectively, while the binding entropies are 41.7 and 15.2 cal/mol·K, respectively. The underlying thermodynamics of binding to AT sites in the minor groove plays a key role in the recognition process. It was also observed that DB75 binding with poly(dA)·poly(dT) can induce T·A·T triplet formation and the compound binds strongly to the dT·dA·dT triplex.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

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Sequence and length dependent thermodynamic differences in heterocyclic diamidine interactions at AT base pairs in the DNA minor groove

Liu

Kumar

Boykin

et al. 2007

Biophysical Chemistry

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“…51 Displacement of bound water from the minor groove in AT sequences provides a general favorable contribution to the binding entropy. 49,[52][53][54] The netropsin structure led the Lown 48,55 and Dickerson 49 groups to propose an extension of the model in which GC base pair specificity could be designed into minor groove binding polyamides by replacing some of the hydrogen bond donating groups on the concave face of the compounds with hydrogen bond acceptors. Such acceptors would be sterically able to accommodate the extra size of the G-NH 2 group, which hydrogen bonds with C in the minor groove, and could form an extra hydrogen bond with the -NH 2 group.…”

Section: Discussionmentioning

confidence: 99%

“…Binding of DB75 and related concave diamidines to AT sites in a 1:1 complex, in contrast, is entropy driven. 52 Thus, both the interaction sequence and the thermodynamic driving force are completely different for DB1242 relative to classical minor groove agents. Interestingly, the DB75 benzimidazole derivative, DB293 (Figure 1), also forms a 2:1 complex in the sequence -ATGA-that has one GC base pair.…”

Section: Discussionmentioning

confidence: 99%

Design of DNA Minor Groove Binding Diamidines That Recognize GC Base Pair Sequences: A Dimeric-Hinge Interaction Motif

et al. 2007

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The classical model of DNA minor groove binding compounds is that they should have a crescent shape that closely fits the helical twist of the groove. Several compounds with relatively linear shape and large dihedral twist, however, have been found recently to bind strongly to the minor groove. These observations raise the question of how far the curvature requirement could be relaxed. As an initial step in experimental analysis of this question, a linear triphenyl diamidine, DB1111 and a series of nitrogen tricyclic analogues were prepared. The goal with the heterocycles is to design GC binding selectivity into heterocyclic compounds that can get into cells and exert biological effects. The compounds have a zero radius of curvature from amidine carbon to amidine carbon but a significant dihedral twist across the tricyclic and amidine-ring junctions. They would not be expected to bind well to the DNA minor groove by shape-matching criteria. Detailed DNaseI footprinting studies of the sequence specificity of this set of diamidines indicated that a pyrimidine heterocyclic derivative, DB1242, has remarkable binding specificity for a GC rich sequence, -GCTCG-. It binds to the GC sequence more strongly than to the usual AT recognition sequences for curved minor groove agents. Other similar derivatives did not exhibit the GC specificity. Biosensor-surface plasmon resonance and isothermal titration calorimetry experiments indicate that DB1242 binds to the GC sequence as a highly cooperative stacked dimer. Circular dichroism results indicate that the compound binds in the minor groove. Molecular modeling studies support a minor groove complex and provide an inter-compound and compound-DNA hydrogen bonding rational for the unusual GC binding specificity and the requirement for a pyrimidine heterocycle. This compound represents a new direction in development of DNA sequence specific agents and it is the first non-polyamide, synthetic compound to specifically recognize a DNA sequence with a majority of GC base pairs.

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Studies on the Unique RNA Duplex Destabilization by an Azoniacyclophane − NMR Titrations with Mono- and Oligonucleotides of the RNA and DNA Types

et al. 2002

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The mechanism of the unique destabilization of a folded RNA by the azoniacyclophane CP66 has been investigated by complexation studies with mono-and short singlestranded oligonucleotides as models. For the mononucleotides, NMR titrations revealed only a slight difference of binding free energy ∆G between RNA-type nucleotides compared to DNA analogues, with ∆∆G values of up to 1.3 kJ/ mol. The complexation-induced NMR shifts (CIS values) both in the ligand and in the cyclophane were also similar for deoxyribo-and ribonucleotides, suggesting similar inclusion geometries in both series. Similar observations had been made earlier on the CIS effects of denatured single-strand polymers. Titrations with dinucleotides showed a slight preference for ribose derivatives, with ∆G = −11.2 kJ/mol for ApA and −13.2 kJ/mol for ApG, and −9.9 kJ/mol for dApdA. With the dinucleotides and with selected tri-and tetranucleotides,

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A thermodynamic and structural analysis of DNA minor-groove complex formation 1 1Edited by I. Tinoco

Cited by 128 publications

References 50 publications

Sequence and length dependent thermodynamic differences in heterocyclic diamidine interactions at AT base pairs in the DNA minor groove

Sequence and length dependent thermodynamic differences in heterocyclic diamidine interactions at AT base pairs in the DNA minor groove

Design of DNA Minor Groove Binding Diamidines That Recognize GC Base Pair Sequences: A Dimeric-Hinge Interaction Motif

Studies on the Unique RNA Duplex Destabilization by an Azoniacyclophane − NMR Titrations with Mono- and Oligonucleotides of the RNA and DNA Types

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