Multisite inhibitors

Saw palmetto s benefits in treatment of BPH are hypothesized to be due in part to antiandrogen effects (Wilt et al., 1998). Saw palmetto is a multisite inhibitor of androgen action. In an in vitro study (Briley et al., 1983), a liposterolic saw palmetto extract called Permixon was shown to compete with... 

U. avenae (Buchenauer, 1977 Dohler and Lempke, 1979). Fenarimol interfers at several synthesis sites, resulting in incomplete membrane structure and thus disturbed membrane function. Fenarimol is thus a multisite inhibitor, so that the development of resistance is not expected from present information. Pyrimidin-5-yl methanols, as a group, are of interest not only because of their antifungal activity, but also because of their growth regulatory activity in higher plants (Sisler et al., 1984). 

Reference will be made to several herbicides which can be classed as multisite inhibitors. Many of these herbicides have clearly established primary target sites. Examples of such herbicides are the hydroxyben-zonitriles and dinitrophenols, which inhibit and uncouple photosynthetic electron transport (see Chapter 1). However, they are clearly mitochondrial electron transport inhibitory uncouplers (Section 5.1), which is accepted as contributing to their overall mode of action, and their inclusion here is justified. 

It is not inconceivable that such permeability effects are a result of an initial direct effect of herbicide binding to ATPase or an electron transport chain component and/or a protonophore action. However, most, if not all, the herbicides discussed in this section can be classed as multisite inhibitors as evidenced by their inclusion in previous chapters, particularly Chapter 1, and elsewhere in this chapter. Such a membrane partitioning would not be specific to the inner mitochondrial membrane but would occur in other... 

Most fungicides developed for plant disease control before 1965 are multisite biochemical inhibitors that lack the chemical properties and biological specificity required for internal therapeutic action in higher plants. This group of plant protectants include such compounds as the Inorganic copper fungicides, captan, chlorothalonil, dithiocarbamates and chlorinated quinones. 

It is difficult to study unisite catalysis directly, since it is some 10 times slower than multisite catdysis. One approach has been to prevent coopoation in Fi, either by working at very low ATP concentrations (when only one catalytic site is occupied) or by adding a specific inhibitor of cooperative interactions such as azide [3]. 

Extract the data using a DNA microarray data analysis software package and analyse the initial velocity data according to standard competitive inhibitor enzyme kinetics using a biphasic multisite model in order to determine the k for the binding of the unlabelled test compound to CYP3A4. 

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