DNA-Compound Interactions

Single-stranded amino-linked DNA or label-free short DNA sequences are bound to these groups by their amino tags [21] and deoxyguanosine residues, respectively [20]. 

On the other hand, covalent agents can also be applied to the unpreated carbon surface directly before DNA immobilization onto activated sites of carbodiimide compounds [21]. 

3 DNA immobilization onto Transducer Surfaces via Avidin-Biotin interaction 

Biotin binds very tightly to the tetrameric protein avidin (also streptavidin and neutravidin], with a dissociation constant in the order of 10, which is one of the strongest known protein-ligand interactions, the strength being approximately due to the the 

Voltammetric methods can be used for (1) the identification of DNA strand breakage and damage, and (2) the determination of electroactive compounds that specifically bind to DNA (covalently and/or noncovalently) [23]. For these purposes, electrochemical DNA biosensors based on the investigation of DNA-compound interactions has been extensively studied with a number of different techniques in the past 15 years and this subject has attracted increasing attention due to its important roles in living organisms toward the aim of inexpensive and rapid analysis in molecular biology. 

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The second label also may be a fluorescent compound, but doesn t necessarily have to be. As long as the second label can absorb the emission of the first label and modulate its signal, binding events can be observed. Thus, the two labeled DNA probes interact with each other to produce fluorescence modulation only after both have bound target DNA and are in enough proximity to initiate energy transfer. Common labels utilized in such assay techniques include the chemiluminescent probe, N-(4-aminobutyl)-N-ethylisoluminol, and reactive fluorescent derivatives of fluorescein, rhodamine, and the cyanine dyes (Chapter 9). For a review of these techniques, see Morrison (1992). 

Work with the carcinogen acetylaminofluorene found that residues of the compound in ribosomal RNA may correlate more closely with liver tumor formation than residues in DNA. Direct interactions with the mechanisms of protein synthesis, or with DNA and RNA polymerase enzymes, can also be seen as possible mechanisms. For instance, a modification of the polymerase enzymes by a carcinogen, either directly or indirectly, could lead to the erroneous replication of DNA or RNA and hence the permanent incorporation of a mutation. 

Members of this group feature tricyclic carbon framework decorated with two oligosaccharide chains. Mithramycin 48 and chromomycin A3 49 are two aureolic acids that have found their use in cancer chemotherapy. These compounds, interacting with Mg2+, bind GC-rich DNA in a nonintercalative way, and sugar chains are indispensable in stabilizing metal-antibiotic complexes. Carbohydrates are... 

Dibenz[a,fi]anthracene is metabolically activated by the mixed function oxidase (MFO) system of the liver (P448) to form an epoxide that subsequently covalently binds to the DNA. This interaction with the DNA is believed to result in the carcinogenicity of the material. The particular area of the compound oxidized by the MFO system will result in epoxides of varying carcinogenic potency. 

An example of the investigation of organotin compounds with deoxyribonucleic acid (DNA), the interaction of two moderately water-soluble anti-tumor organotins, " bis[(di-n-butyl-3,6-dioxaheptanoato)tin]... 

Because the cell surface is negatively charged, positively charged compounds interact more intensely with cells than do negatively charged ones. Cationic complexes of plasmid DNA with any cationic vector exhibit very different pharmacokinetic profiles from that of naked plasmid DNA. They avidly bind to endothelial cells and normally accumulate in the lung after intravenous injection due to the first-pass effect.22,23... 

A different nucleic acid sensor, not based on the hybridization reaction, can be developed by immobilizing a nucleic acid sequence which acts as capturing receptor for a molecule in solution (i.e., a protein). The probe shows an affinity for the target analyte and binds it, when present in solution. This system can be applied for studying DNA-protein interaction [9], or to show the ability of different chemical compounds (intercalators) to bind DNA [10]. The binding is driven by the affinity of the nucleic acid sequence for the target molecule. 

Therefore, it is not surprising that the fascination of fluorine entered the field of anthracycline glycoside synthesis. Remarkable chemical interest consequently arose on the introduction of fluorine into the anthracycline molecule with the aim of altering the biorelevance of functional groups, thus providing new compounds whose DNA-drug interaction and antitumor properties could be compared with those exhibited by the clinically used an-thracyclines (1-4) (Fig. 1). 

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