Intercalation into DNA

Nakatani, K. Matsuno, T. Adachi, K. Hagihara, S. Saito, I. Selective intercalation of charge neutral intercalators into GG and CG steps implication of HOMO-LUMO interaction for sequence-selective drug intercalation into DNA. J. Am. Chem. Soc. 2001, 123, 5695-5702. 

A crystal structure of Rh(lll) phi complex intercalated into DNA high resolution NMR... 

The DNA binding of [cp Ir(dppz)(Aa)]"+, dppz = dipyrido[3,2-a 2, 3 -c]phenazine, Aa = S-coor-dinated amino acid or peptide, has been investigated by UV-vis spectroscopy, 2D-NOESY, and gel electrophoresis. The complexes intercalate into DNA adjacent to T2 from the major groove. The X-ray structural data for [cp IrCl(dppz)](CF3S03)4 and [ cp Ir(9-EtG)(Phen)](CF3S03)2, where GH = guanine, are reported.423... 

The fluorescence of BaPT OS) and of other related compounds (40) seems to be nearly completely quenched upon physical intercalation into DNA. 

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... 

The non-covalently bound BPDEs to DNA formed initially appear to be intercalation complexes (1 6,52-55) Meehan et al. (1 6) report that the BPDE intercalates into DNA on a millisecond time scale while the BPDE alkylates DNA on a time scale of minutes. Most of the BPDE is hydrolyzed to tetrols (53-56). Geacintov et al. (5l ) have shown with linear dichroism spectral measurements that the disappearance of intercalated BPDE l(+) is directly proportional to the rate of appearance of covalent adducts. These results suggest that either there may be a competition between the physically non-covalently bound BPDE l(+) and an externally bound adduct or as suggested by the mechanism in the present paper, an intercalative covalent step followed by a relaxation of the DNA to yield an externally bound adduct. Their results for the BPDE i(-) exhibit both intercalative and externally bound adducts. The linear dichroism measurements do not distinguish between physically bound and covalent bound forms which are intercalative in nature. Hence the assumption that a superposition of internal and external sites occurs for this isomer. 

The use of an extended arene (tetrahydroanthracene) in [OsCl(en)(ri6-tha)]+ (29) gave rise to a similar potency (112). This is in contrast with the data for ruthenium-arenes, where the same substitution gave rise to a 10-fold increase in activity. Further work therefore needs to determine if the extended Os-arenes can intercalate into DNA in a manner similar to Ru-arenes. Replacement of the iV /V-chelating ligand en for other AyV-bidentates with pyridine, aliphatic amine, or azopyridine donor atoms leads to loss of activity, probably because of slower hydrolysis and higher acidity of the coordinated water (112). 

P. Cieplak, S. N. Rao, P. D. J. Grootenhuis, and P. A. Kollman, Free energy calculation on base specificity of drug-DNA interactions Application to daunomycin and acridine intercalation into DNA, Biopol. 29 717 (1990). 

Only a few studies of RET in one dimension - between dyes intercalated into DNA - have been reported. 

The values of the binding constants determined with different salt concentrations by equilibrium dialyses [43, 48], luminescence titrations and electrochemiluminescence [82], are all 2 or 3 orders of magnitude lower than for ethidium bromide. Therefore, a priori, they do not indicate contribution of classical intercalation into DNA as described for organic molecules and for the DPPZ, HAT and PPZ complexes. 

Amsacrine (m-AMSA) is a synthetic aminoacri-dine which intercalates into DNA and inhibits DNA topoisomerase II. m-AMSA is not cross-resistant to anthracyclines and has been particularly active in acute non-lymphocytic leukemia. Amsacrine is administred by intravenous infusion. It is metabolized in the liver and eliminated in the bile with an elimination half-life of 6-9 hours. Its major toxicity is bone marrow depression. Gastrointestinal disturbances are frequent. Neurotoxicity and cardiotoxic-ity may occur. 

It is an erythrocytic schizontocide related to its ready intercalation into DNA. 

Daunorubicin Oxygen free radicals bind to DNA causing single- and double-strand DNA breaks inhibits topoisomerase II intercalates into DNA AML, ALL Nausea, fever, red urine (not hematuria) Cardiotoxicity (see text), alopecia, myelosuppression... 

Figure 5-22 Structures of some substances that tend to "intercalate" into DNA structures. See also Fig. 5-23.

Since the 1950s, using a different approach, the U.S. National Cancer Institute, as well as agencies in other countries, has sought to find natural anticancer compounds in plants, fungi, microorganisms, and marine invertebrates. Among these are many antibiotics that intercalate into DNA helices, e.g.,... 

How do antibiotics act Some, like penicillin, block specific enzymes. Peptide antibiotics often form complexes with metal ions (Fig. 8-22) and disrupt the control of ion permeability in bacterial membranes. Polyene antibiotics interfere with proton and ion transport in fungal membranes. Tetracyclines and many other antibiotics interfere directly with protein synthesis (Box 29-B). Others intercalate into DNA molecules (Fig. 5-23 Box 28-A). There is no single mode of action. The search for suitable antibiotics for human use consists in finding compounds highly toxic to infective organisms but with low toxicity to human cells. 

Fluorescence assays are considered among the most convenient, sensitive, and versatile of all laboratory techniques. However, the purine and pyrimidine bases yield only weak fluorescence spectra. Le Pecq and Paoletti (1967) showed that the fluorescence of a dye, ethidium bromide, is enhanced about 25-fold when it interacts with DNA. Ethidium bromide, which is a relatively small planar molecule (Figure El3.4), binds to DNA by insertion between stacked base pairs (intercalation). The process of intercalation is especially significant for aromatic dyes, antibiotics, and other drugs. Some dyes, when intercalated into DNA, show an enhanced fluorescence that can be used to detect DNA molecules after gel electrophoresis measurements (see Chapter 4 and Experiments 14 and 15) and to characterize the physical structure of DNA. Two analyses of DNA will be completed in this experiment ... 

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