Small molecule drug

Until now, microorganisms such as fungi and bacteria (often extremophiles) were used as main sources for enzymes. The growing complexity of reactions required for the production of fine chemicals, especially for the pharmaceutical industry, has increasingly drawn the attention of industrial biotechnology to plants. The high complexity of plants secondary metaboHsm, as well as the fact that most of today s small molecule drugs (SMDs) can be traced back to a plant metabolite as the basic structure, is certainly a major reason for this development Moreover, 

As most secondary metabolites are only made in low amounts and are often found in wild-type plants not optimized for cultivation, supply of the desired molecule is often limited or at least very costly. To overcome this bottleneck, different ways have been developed to produce important metabolites or precursors in cell cultures, tissue cultures, or in higher amount in whole plants [44], PacUtaxel (an anticancer agent) is one of these substances with high commercial value where independently estabUshed suspension cultures of genetically engineered plant cells have been patented as production process [52, 53). 

Combinatorial biosynthesis, that is, the combination of metabolic pathways in different organisms on a genetic level allowing the use of precursors of the host cells is another promising strategy for the synthesis and industrial production of important classes of natural products, including alkaloids (vinblastine, vincristine), terpenoids (artemisinin, pacUtaxel), and flavonoids [59], 

Another alkaloid whose production has been successfully improved by genetic engineering in plant cell culture and whole plants is benzylisoquinohne. This was done in poppy plants and cell cultures by RNAi inhibition of the berberme bridge enzyme, which resulted in the production of reticuline [61]. The same enzyme was also targeted in an approach to transfer the benzylisoquinohne alkaloid production from tyrosine in the Papaveraceae, Berberidaceae, Ranunculaceae, Magidiaceae, and other plant famUies into microorganisms [62]. Its transfer in yeast resulted in the 

---

While some biological targets such as DNA are not protein in nature, most receptors are. It is useful to consider the properties of receptor proteins to provide a context for the interaction of small molecule drugs with them. An important property of receptors is that they have a 3D structure. Proteins usually are comprised of one or... 

Jang GR, Harris RZ, Lau DT. Pharmacokinetics and its role in small molecule drug discovery research. Med Res Rev 2001 21 382-96. 

The attractiveness of enzymes as drug targets results not only from the essentiality of their catalytic activity but also from the fact that enzymes, by their very nature, are highly amenable to inhibition by small molecular weight, drug-like molecules. Because of this susceptibility to inhibition by small molecule drugs,... 

Figure 1.2 Worldwide market for small molecule drugs that function as enzyme inhibitors in 2001 and projected for 2006. AAGR = average annual growth rate.

Recently, the LbL technique has been extended from conventional nonporous substrates to macroporous substrates, such as 3DOM materials [58,59], macroporous membranes [60-63], and porous calcium carbonate microparticles [64,65], to prepare porous PE-based materials. LbL-assembly of polyelectrolytes can also be performed on the surface of MS particles preloaded with enzymes [66,67] or small molecule drugs [68], and, under appropriate solution conditions, within the pores of MS particles to generate polymer-based nanoporous spheres following removal of the silica template [69]. 

TABLE 12.2 Comparison of Protein Therapeutic Agents with Small Molecule Drugs... 

There has been significant advancement in the applications of NMR to the development of small-molecule pharmaceutical products. For example, advances in NMR automation (e.g., flow-injection analysis) and directly coupled methods (e.g., LC-MS-NMR analysis) have made analysis and characterization of small-molecule drugs much easier.23 25 These improvements have helped chemists to develop and characterize small-molecule combinatorial libraries and to screen for active compounds.4 6 It is likely some of these techniques can also be used in biopharmaceutical product development. 

There are two main approaches to discovering small molecule drugs the irrational approach or the more recent structured rational approach. Antisense, RNA interference, and chiral drugs are other drug discovery methodologies. 

---