Theoretical studies of drug-dinucleotide interactions. Empirical energy function calculations on the interaction of ethidium, 9-aminoacridine, and proflavin cations with the base-paired dinucleotides GpC and CpG

Nuss, Merrill E.; MARSH, F. J.; Kollman, Peter A.

doi:10.1021/ja00498a008

Cited by 87 publications

(34 citation statements)

References 7 publications

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“…These showed that, in DNA as well as in RNA, intercalation into the pyrimidine-3' ,5'-purine sequence is 7 to 13 kcallmole more favorable than purine-3' ,5'-pyrimidine intercalation because base-intercalator overlap is more pronounced in the pyrimidine-(3'-5')-purine sequence than in the reversed one (1119). This intermolecular interaction is supported by intra molecular electrostatic forces rendering pyrimidine -3' ,5' -purine sequences more prone to intercalation (1115). In addition, stereochemically unfavorable interactions may playa role if the reversed base sequence is employed (1115,1117).…”

Section: Stereochemistry Of Intercalation Into Dna-and Rna-type Dinucmentioning

confidence: 99%

Principles of Nucleic Acid Structure

Saenger

1984

Springer Advanced Texts in Chemistry

5,967

312

6,279

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Section: Stereochemistry Of Intercalation Into Dna-and Rna-type Dinucmentioning

confidence: 99%

Principles of Nucleic Acid Structure

Saenger

1984

Springer Advanced Texts in Chemistry

5,967

312

6,279

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“…17,18 It exhibits distinctive mutagenic activity 19 ability to interact with DNA 22−28 and other biologically important molecules. 24,29,30 It also appears to be a convenient probe for investigating various physical features of biological systems. 31,32 Therefore, it is important to know whether simple derivatives of acridin-9-amine which have fixed structures of both tautomeric forms can be synthesized and investigated experimentally, and what impact the structure may have on their properties, including biological activity.…”

Section: Introductionmentioning

confidence: 99%

X-Ray, Quantum Mechanics and Density Functional Methods in the Examination of Structure and Tautomerism of N-Methyl-Substituted Acridin-9-amine Derivatives

Rak¹,

Krzymiński²,

Skurski³

et al. 1998

Aust. J. Chem.

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X-Ray diffraction has shown that N,N-dimethylacridin-9-amine (4) and N ,10-dimethylacridin-9-imine (5) both crystallize in the monoclinic space group P21/c (No. 14) with four molecules in the unit cell. The dimethylamino group in (4) is twisted through an angle of 58·6° relative to a nearly planar acridine moiety. On the other hand, the central ring in (5) is folded along the C(9) · · · N(10) axis through an angle of 26·3° and the exocyclic nitrogen atom with the methyl group attached to it is directed away from the concave side of the acridine nucleus. Theoretical ab initio Hartree–Fock (HF) and semiempirical (MNDO, AM1, PM3) quantum mechanics, as well as density functional (DFT) methods predicted that the N,N-dimethylacridin-9-amine molecule is planar within the acridine moiety and exhibits Cs symmetry, while the other four derivatives originating from the amino or imino tautomeric forms of acridin-9-amine do not have any symmetry elements. Molecules retaining the amino constitution are thermodynamically somewhat more stable than those arising from the imino form. The negative LUMO and HOMO energies, both predicted at the semiempirical level of theory and at the HF level in the latter case, imply that the relevant states are electronically stable. The comparable thermodynamic stabilities of both types of derivatives, as well as the fact that they can be synthesized, undoubtedly speak in favour of the existence of tautomeric phenomena in acridin-9-amine

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“…This is so because a large number of studies, including significant theoretical contributions (17)(18)(19) …”

Section: Introductionmentioning

confidence: 99%

A Theoretical Investigation on the Sequence Selective Binding of Daunomycin to Double-Stranded Polynucleotides

Chen

Gresh

Pullman

1985

Journal of Biomolecular Structure and Dynamics

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Theoretical computations are performed on the structural and energetical factors involved in the sequence selective binding of daunomycin (DNM) to six representative self-complementary double-stranded hexanucleotides: d(CGTACG)2,d(CGATCG)2,d(CITACI)2, d(TATATA)2, d(CGCGCG)2 and d(TACGTA)2. The conformational angles of the hexanucleotides are fixed in values found in the representative crystal structure of the d(CGTACG)2-DNM complex. The intermolecular DNM-hexanucleotide interaction energies and the conformational energy changes of DNM upon binding are computed and optimized in the framework of the SIBFA procedure, which uses empirical formulas based on ab initio SCF computations. Among the two regularly alternating hexanucleotides, d(TATATA)2 and d(CGCGCG)2, a stronger binding is predicted for the former, in agreement with experimental results obtained with poly(dA-dT).poly(dA-dT) and poly(dG-dC).poly(dG-dC). Altogether, however, among the six investigated sequences, the strongest complexes are computed for the mixed hexanucleotides d(CGATCG)2 and d(CGTACG)2, containing the intercalation site between two CG base pairs and an adjacent TA base pair. This situation may be related to the increased affinity of DNM for GC rich DNA's and to the situation in the crystal structure of the DNM-d(CGTACG)2 complex. Analysis of the intrinsic base sequence preferences expressed by the individual constituents of DNM, namely the daunosamine side chain, the chromophore ring and its two 9-hydroxyl and 9-acetoxy substituents, reveals that the overall sequence preference found is the result of a rather intricate interplay of intrinsic sequence preferences, in particular at the level of daunosamine and the 9-hydroxyl substituent.(ABSTRACT TRUNCATED AT 250 WORDS)

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Theoretical studies of drug-dinucleotide interactions. Empirical energy function calculations on the interaction of ethidium, 9-aminoacridine, and proflavin cations with the base-paired dinucleotides GpC and CpG

Cited by 87 publications

References 7 publications

Principles of Nucleic Acid Structure

Principles of Nucleic Acid Structure

X-Ray, Quantum Mechanics and Density Functional Methods in the Examination of Structure and Tautomerism of N-Methyl-Substituted Acridin-9-amine Derivatives

A Theoretical Investigation on the Sequence Selective Binding of Daunomycin to Double-Stranded Polynucleotides

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