4 Dynamics of DNA Supercoiling 634.2.4 Dynamics of Drug Targeting
The FLD technique can prove very useful in studies of the interactions of en-
zymes of topoisomerisation with various inhibitors and poisons [33, 34]. Such
effectors are of great interest because of their high anti-tumour activity [35]. As
an example, we have chosen a number of relatively well-studied compounds,
some of them are already applied as anti-cancer drugs. For topoisomerase
I, camptothecin (CPT) and two of its analogues, MCPT-10,11 and SN-38
(see Fig. 4.13) were taken, which are known to inhibit the process on the stage
Fig. 4.13.Inhibition of topoisomerase I by specific effectors studied by FLD tech-
nique. Experimental conditions: Effect of increasing concentrations of several camp-
tothecine analogues on the kinetics of topoisomerisation of pTM DNA (8μg) by
topoisomerase I (0. 45 μg): (a) 0, 0.25, 0.5, 0.75, 1.25, 12. 5 μMCPT;(b) 0, 0.05,
0.075, 0.125, 0.25μM MCPT-10,11; (c) 0, 0.075, 0.15, 0.2, 0. 25 μM SN-38. Insets:
enlarged initial parts of the curves