Comparative binding study of the interaction of quinacrine and ethidium bromide with DNA and nucleohistone

Bontemps, José; Frédéricq, E.

doi:10.1016/0301-4622(74)80019-0

Cited by 46 publications

(13 citation statements)

References 53 publications

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“…Absorption changes induced upon binding of (Tp)n(CH2)5Acr to poly(rA) are quite similar to those observed when quinacrine binds to double-stranded nucleic acids (14). A strong hypochromism is observed together with a red-shift of the absorption spectrum whose amplitude depends upon the nucleic acid base sequence and the duplex structure.…”

Section: Resultssupporting

confidence: 49%

Nucleic acid-binding molecules with high affinity and base sequence specificity: intercalating agents covalently linked to oligodeoxynucleotides.

Asseline¹,

Delarue²,

Lancelot³

et al. 1984

Proc. Natl. Acad. Sci. U.S.A.

181

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Oligodeoxyribonucleotides covalently linked to an intercalating agent via a polymethylene linker were synthesized. Oligothymidylates attached to an acridine dye (Acr) through the 3'-phosphate group [(Tp),(CH2)mAcr] specifically interact with the complementary sequence. The interaction is strongly stabilized by the intercalating agent. By using absorption and fluorescence spectroscopies, it is shown that complex formation between (Tp),(CH2)mAcr and poly(rA) involves the formation of n A-T base pairs, where n is the number of thy. mines in the oligonucleotide. The acridme ring intercalates between ANT base pairs. Fluorescence excitation spectra reveal the existence of two environments for the acridine ring, whose relative contributions depend on the linker length (m). The binding of (Tp)4(CH2)mAcr to poly(rA) is analyzed in terms of site binding and cooperative interactions between oligonucleotides along the polynucleotide lattice. Thermodynamic parameters show that the covalent attachment of the acridine ring strongly stabilizes the binding of the oligonucleotide to its complementary sequence. The stabilization depends on the linker length; the compound with m = 5 gives a more stable complex than that with m = 3. These results open the way to the synthesis of a family of molecules exhibiting both high-affinity and high-specificity for a nucleic acid base sequence.Molecules with high affinity and base-sequence specificity are required to control gene expression at different levels. Several possibilities may be contemplated depending on whether double-stranded or single-stranded nucleic acids are chosen as targets. For example, the regulation of transcription involves proteins that recognize specific duplex DNA sequences in both prokaryotes and eukaryotes (1, 2). However, there is no general rule yet established that could allow us to build an oligopeptide sequence aimed at recognizing a given base or base pair sequence (3). Moreover, the amino acid side chains that are involved in contacts with base or base pairs are not contiguous in the polypeptide chain.The most obvious candidate to allow for the specific recognition of a nucleic acid fragment is an oligonucleotide with the complementary sequence, provided the nucleic acid bases in the target sequence have their hydrogen bonding sites available. This is obviously so if the target nucleic acid region exists as a single-stranded structure. This might also be true in a duplex structure if a sufficient supplementary energy of interaction were provided either by modifying the oligonucleotide (see below) or by imposing constraints on the duplex structure (e.g., in superhelical DNA or upon binding of melting proteins). Also it must be kept in mind that important regulatory regions in transcription and replication must be transiently opened as observed-e.g., in the complex formed by bacterial RNA polymerase with a promoter (the so-called "open complex") (4) or at the replication fork (5). Actively transcribed genes in eukaryotes also possess regions upstream f...

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Section: Resultssupporting

confidence: 49%

Nucleic acid-binding molecules with high affinity and base sequence specificity: intercalating agents covalently linked to oligodeoxynucleotides.

Asseline¹,

Delarue²,

Lancelot³

et al. 1984

Proc. Natl. Acad. Sci. U.S.A.

181

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“…A typical Scatchard analysis of the binding of T4MPyP to DNA is shown in figure 3 as a plot of r/m versus r. The letter r represents the number of moles of porphyrin bound/mole of DNA base pairs, and m is the concentration of unbound porphyrin. The general shape of the curve is indicative of complex binding, which may be treated using a nuniLer of available models (14). Evidence to be presented from our circular dichroism and melting profile experiments suggests that two binding sites or binding modes are involved at the moderate ionic strength of BPES buffer.…”

Section: A Spectroscopymentioning

confidence: 88%

“…Concluding that a particular compound binds to DNA by intercalation usually indicates that its properties are known to be similar to those of established intercalating agents, such as, ethidium bromide (14) or proflavine (2). On this basis, as is evident from the results already presented, we have concluded that T4MPyP can be classified as an intercalating agent.…”

Section: Discussionmentioning

confidence: 99%

Interaction of DNA with a porphyrin ligand: evidence for intercalation

Fiel¹,

Howard²,

Mark³

et al. 1979

Nucl Acids Res

349

282

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“…Although it has been established that ethidium has a preference for binding to pyrimidine(3'-5') purine sequences when compared to purine(3'-5')pyrimidine sequences (9)(10) it has also been shown that the apparent binding affinity of ethidium is not very dependent upon the overall base composition (1-2, 13). The equilibrium binding of ethidium to various native DNAs has been reported (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12), with the binding isotherms presented in these papers being well represented by the nearest neighbor exclusion model (14)(15) Volume 10 Number 24 1982 and Young (16) which showed that daunorubicin and adriamycin facilitated the binding of actinomycin D to poly(dA-dT). poly(dA-dT), a polynucleotide to which actinomycin D does not bind.…”

Section: Introductionmentioning

confidence: 96%