Targets of Secondary Metabolites

Among broadly active alkaloids, a distinction can be made between those that are able to form covalent bonds with proteins and nucleic acids, and those which modulate the conformation of proteins and nucleic acids by non-covalent bonding. Covalent bonds can be formed with reactive functional groups of SM, such as 

Molecular targets in animal and human cells that can be affected by natural 

Lipophilic compounds, such as the various terpenoids, tend to associate with other hydrophobic molecules in a cell these can be biomembranes or the hydrophobic core of many proteins and of the DNA double helix (4,13,14). In proteins, such hydrophobic and van der Waals interactions can also lead to conformational changes, and thus protein inactivation. A major target for terpenoids, especially saponins, is the biomembrane. Saponins can also change the fluidity of biomembranes, thus reducing their function as a permeation barrier. Saponins can even make cells prone to leak, which immediately leads to cell death. This can easily be seen in erythrocytes when they are attacked by saponins these cells burst and release hemoglobin (hemolysis) (4,13,14). 

These pleiotropic, multitarget bioactivities are not specific, but are nevertheless effective, and this is what is critical in an ecological context. Compounds with pleiotropic properties have the advantage that they can attack any enemy that is encountered by a plant, be it a herbivore, a bacterium, fungus, or virus. These classes of compounds are seldom unique constituents quite often plants produce a mixture of SM, often both phenolics and terpenoids, and thus exhibit both covalent and non-covalent interactions. These activities are probably both additive, and s3mergistic (13,14). 

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It is of particular interest that polyamines closely related to CNS 2103 have been found not only in other spider species (29) but also in the venom of the solitary digger wasp Philanthus triangulum (32). The similarity of these wasp and spider neurotoxins provides a notable example of convergence in the evolution of secondary metabolites aimed at a common target. 

Plant cell culture is useful in laboratory and in industry because it allows plant natural products to be produced in a relatively controlled manner, and provides a supply of plant material that is not affected by sourcing problems, such as environmental, seasonal, geographical, and political factors.Also, plant cell culture allows for the tweaking and rearrangement of secondary metabolite biochemical pathways in order to produce novel metabolites, and to increase target compound yields, as well as allowing derivatives to be formed by introduction of analogs of natural intermediates.Plant cell culture can be performed with callus and suspension cultures, as well as with shoot cultures and hairy root cultures. These latter two approaches are especially useful when a metabolite is found to be produced more readily in differentiated cells. 

Allergenic effects. A number of secondary metabolites influence the immune system of animals, such as coumarins, furanocoumarins, hypericin, and helenalin. Common to these compounds is a strong allergenic effect on those parts of the skin or mucosa that have come into contact with the compounds (4,17,312). Activation or repression of the immune response is certainly a target that was selected during evolution as an antiherbivore strategy. The function of alkaloids in this context is hardly known. 

A number of different methods for stable or transient genetic transformation of plants or plant cells have been developed [13-15]. These comprise particle bombardment, Agro actermm-mediated transformation, floral dip transformation, agrodrench, viral vectors, protoplast transformation and ultrasound. These are the main techniques for the genetic transformation of plants, and many of them have also been applied for the transformation of secondary metabolite pathways in an attempt to alter the metabolic pathways of target... 

Figure 1 The retrobiosynthetic principle. Labeling patterns of central metabolic intermediates (shown in yellow boxes) are reconstructed from the labeling patterns of sink metabolites, such as protein-derived amino acids, storage metabolites (starch and lipids), cellulose, isoprenoids, or RNA-derived nucleosides. The reconstruction is symbolized by retro arrows following the principles of retrosynthesis in synthetic organic chemistry. The figure is based on known biosynthetic pathways of amino acids, starch, cellulose, nucleosides, and isoprenoids in plants. The profiles of the central metabolites can then be used for predictions of the labeling patterns of secondary metabolites. In comparison with the observed labeling patterns of the target compounds, hypothetical pathways can be falsified on this basis.

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