Intercalating drugs

In order to understand the interactions between these bis-intercalating drugs and IMA more fully, we have crystallized several complexes of them and undertaken the structure determination by x-ray diffraction technique. One of the crystal forms diffracts to 1.6 A resolution with a space group of F222. The crystal structure was determined by the multiple isomorphous replacement method using three different heavy atom derivatives. The structure was refined to an R-factor of 19% and there were moderate number of solvent molecules clearly visible. The crystal... 

The intercalating drugs and nucleic acid synthesis inhibitors discussed in the preceding sections interfere indirectly with every phase of nucleic acid action because the DNA is rendered nonfunctional. Other drugs, discussed below, affect the regulation of protein synthesis even when the genome, the DNA structure, is intact. Such activity can be the result of interference either with transcription of messenger RNA or with translation of the mRNA to protein. 

Fig. 5 Calculated changes in the average rise and roll angle of the separated to the intercalated state transition along the sampling coordinate X. Note that the roll angle increases earlier than the rise as the intercalating drug approaches.

The second class of drugs (intercalating drugs) involves interaction of the two anthra-cycline derivatives aclacinomycin A and violamycin B1 with DNA, which has recently been investigated by infrared linear dichroism (Fritzsche and Rupprecht, 1990). The restriction of the B —> A transition as a consequence of drug binding turns out to be only slightly dependent on the DNA base composition. 

Intercalating drugs are compounds which are capable of slipping between the layers of nucleic acid base pairs and disrupting the shape of the double helix. This disruption prevents replication and transcription. One example is the antibacterial agent proflavine (Fig. 6.6). 

Publications about oligonucleotides linked to acridine derivatives have been summarized by several authors [246,275-277], The intercalating properties of acridine derivatives have been shown by NMR-studies [278, 279], 9-Amino-6-chloro-2-methoxyacridine is mostly used, which differs only slightly in size from the important intercalator drug, psoralen. Acridine-... 

The interaction with small molecules such as metal ions and intercalating molecules has been investigated. Both the molecular nature of the interaction and the influence on the conformation have been addressed. " Infrared linear dichroism has also been applied to the study of intercalating drugs interacting with oriented films of DNA. In many of the cited references normal mode calculations have been performed to provide a molecular basis for the interpretation of the spectra in terms of the different conformers. 

For a review of the biological behaviour of intercalating drugs, see Schwartz (1979). 

In another example of a hybrid DDS, ranitidine hydrochloride, the H2 histamine receptor inhibitor, was intercalated in MMT and coated with the cationic polymer Eudragit ElOO using an oil-in-water solvent evaporation method. The material obtained had the form of microparticles. It vras found that in the presence of Eudragit ElOO, both the release rate and the amount of drug released noticeably increased, because of the effective exchange of the polycation with intercalated drug molecules. In a similar... 

Gale EF, Cundliffe E, Reynolds PE, Richmond MH, Waring MJ (1981) The classical intercalating drugs. In The molecular basis of antibiotic action, 2nd edn. Wiley, London New York, pp 274-306... 

Ultrasonic methods have been used to study the syn anti equilibrium of 2-deoxyadenosine in presence of ethidium bromide and indole-3-acetic acid, which, respectively, serve as models for an intercalating drug and a tryptophan unit at a protein binding site. ... 

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