Intercalative binding

The unmodified and complementary oligonucleotides were also synthesized, in order to detect thermodynamic and spectroscopic differences between the double helices. Circular dichroism spectra revealed that the covalently bound anthracene does not stack in the centre of the DNA double helix. Mutagenic activity by intercalative binding of the anthracene residue is thus unlikely. Only in vitro and in vivo replication experiments with site-specifically modified... 

Electrostatic binding Groove binding Intercalative binding Fig. 5 Schematic representation of various binding modes of small molecules to DNA... 

Graves DE, Velea LM (2000) Intercalative binding of small molecules to nucleic acids. Curr Org Chem 4 915-929... 

For BP metabolites and metabolite model compounds UV absorption experiments provide an independent means by which binding constants for hydrocarbon intercalation into DNA can be measured. Intercalative binding gives rise to a red shift ( 10 nm) in the hydrocarbon UV absorption spectrum of PAH. Figure 7 shows absorption spectra of trans-7,8-dihydroxy-7,8-dihydro-BP at varying... 

Intercalation of BPDE. Several groups have studied the reversible intercalative binding of BPDE to DNA. The fluorescence quantum yield of BPDE is much lower than that of BP derivatives which do not contain an epoxide group and fluorescence techniques have not been widely used to study BPDE physical binding to DNA (4). Association constants for the DNA intercalation of BPDE have been obtained by measuring red shifts in the UV absorption spectra of BPDE which occur upon the formation of intercalated complexes and from fluorescence studies (8) of the kinetics of DNA catalyzed hydrolysis of BPDE. The hydrolysis reaction is conveniently monitored by following the fluorescence of the hydrolysis product, BPT, which has a quantum yield many times greater than BPDE. 

Table IV also contains results of UV absorption studies of hydroxylation effects on the DNA intercalative binding of ben-zo[a]pyrene metabolites and metabolite model compounds. The most important feature of these results is that hydrolysis of BPDE to BPT causes a four-fold reduction in the intercalation association constant. Of all the BP derivatives studied, the tetrol has the lowest binding constant for intercalation. The small binding constant of the tetrol compared with BPDE, coupled with the DNA catalyzed hydrolysis of BPDE to the tetrol may provide a detoxification pathway for removal of a portion of unreacted intercalated BPDE.

Once the site is created, the ability of each BPDE to fit into the receptor is examined. Two processes are considered intercalation and covalent intercalative binding represented by... 

Intercalative binding to DNA is often proposed as a route to enhancing selectivity of anticancer agents, and shape-selective intercalation of ruthenium-polyaromatic amines has been widely used for probing DNA structure (185). This approach could yield new drugs. 

Intercalators associate with dsDNA by insertion between the stacked base pairs of DNA [52], EtBr binds to dsDNA with little to no sequence specificity, with one dye molecule inserting for every 4-5 base pairs [53]. It also binds weakly via a non-intercalative binding mechanism only after the intercalative sites have been saturated [54], Propidium iodide (PRO) is structurally similar to ethidium bromide, and both dyes show a fluorescence enhancement of approximately 20-30 fold upon binding to dsDNA [41]. As well, their excitation maxima shift 30-40 nm upon binding due to the environment change associated with intercalation into the more rigid and hydrophobic interior of the double-stranded nucleic acid structure relative to aqueous solution [41]. 

Daunomycin and adriamycin bind to DNA with similar binding constants of t.2.5 x 10 M- in 0.1 M buffer, pH 7.0 at 20°C, with one anthracycline antibiotic bound per six nucleotides at maximum intercalative binding (80,81). The binding constant is dependent on the salt concentration and decreases by a factor of 5 on proceeding from 0.1 M to 1.0 M NaCl solution (82). 

The fluorescence spectra of chelerythrine, nitidine, and sanguinarine in different solvents have been shown to be dependent on the pH of the solution and to allow the determination of the equilibrium constant for the formation of the pseudobases.531 A salt of chelidonine with 5-carboxymethyl-2-thio-l,3-thiazan-4-one has been prepared.532 The intercalative binding of sanguinarine533 and the anti-tumour activities of chelidonine JV-oxide534 and of nitidine535 have been studied. 

The ability of metal complexes to unwind DNA has been put forth as an important criterion for proving an intercalative binding mode and has been observed with other complexes of phen, dppz, and phi (21, 28,30,33). The enzyme topoisomerase can be used to determine if small molecules unwind DNA, according to published procedures (28). We find that by using this assay, Ru(tpy)(dppz)OH22+ unwinds DNA by 17°, which is consistent with intercalative binding. 

The complexes [Re(CO)3(N-N)(L)]+ (N-N = dppz or dppn (3), L = pyridine or 4-methylpyridine) have been prepared and their luminescence properties studied. Luminescence and transient absorption spectroscopy indicated that this class of complexes exhibited a triplet IL excited state. The intercalative binding of the complexes to double-stranded calf thymus DNA and synthetic oligonucleotides was investigated, and cleavage of the plasmid pBR322 upon visible light irradiation was observed. It appeared that the excited complex [Re(CO)3(dppz)(py)]+ directly oxidized the DNA molecule. However, in the case of the dppn analogue, the... 

Luminescent cyclometalated platinum(II) and gold(III) complexes [Pt(dpp-CNN)(MeCN)]+/ [Pt2(pby-CNN)2 (dppm)] +, and [Au(4-MeOPh-Phbpy)Cl] have been prepared and their interactions with calf thymus DNA and synthetic oligonucleotide duplexes poly(dG-dC)2 and poly(dA-dT)2 have been investigated. An intercalative binding mode was proposed for these complexes. 

The interactions of Cu(n)TMPyP with DNA result in an intercalative binding mode that corresponds to a negative band at 426(-) nm in ECD spectra and a new positive band at 1690(+) cm in VCD spectra. The binding of Cu(ll)TMPyP affects substantially the DNA structure in the GC base-pair regions at higher Cu(n)TMPyP loadings. Intercalative sites are saturated at the 3/1 ratio, which is demonstrated by the fact that VCD and ECD resemble those of poly(dA-dT)2 [112, 135). 

Figure 25 The (a) D2 CG and (b) D3 CG proposed triads forming one and two hydrogen bonds, respectively, (c) Intercalative binding by D3...

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