Strand cleavage selectivity

The guanine radical cations (G +) are detected by their reactions with water, which leads after treatment with piperidine or ammonia to selective strand cleavage [14]. A similar charge detection method was used by J.K. Barton, G.B. Schuster and I. Saito as described in their articles in this volume. The cleavage products were separated and quantified by gel electrophoresis. A typical example is shown in Fig. 7 where the GGG unit acts as a thermodynamic sink for the positive charge, and the efficiency of the charge transfer can be measured by the product ratio Pggg/Pg-... 

Figure 10 shows that the values of kag for the oxidation of G and GG are close to one another, and are smaller by a factor of only -1.7 than the value of kag for the oxidation of guanine in the GGG sequence. Estimates by Lewis et al. [89] have shown that even small differences in the rate constants can provide modest selectivities for alkali-labile strand cleavage observed in a number of experimental studies [83-90]. 

The most striking example of the specificity to be derived from shape-selective targeting has been given by the double-stranded cleavage induced by Rh(DIP)3 at cruciforms. Rh(DIP)3, like its Co(III) and Ru(II) congeners, binds to locally unwound, non-B-conformations such as Z-DNA, but interestingly this potent photooxidant yields the specific cleavage of both DNA strands... 

The mechanism of action of pentamidine is not known with certainty, but strong evidence supports various mechanisms of action for pentamidine. Pentamidine selectively binds to the DNA in trypanosoma parasite (see below). Pentamidine has also been shown to inhibit topoisomerase in Pneumocystis carinii, which leads to double-strand cleavage of DNA in trypanosoma (12,13,14). It has been suggested that pentamidine s mechanism of action may be different in different organisms and, therefore, that the actions reported for trypanosoma may not carry over to pneumocystis. 

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